Monocyte differentiation toward regulatory dendritic cells is not affected by respiratory syncytial virus-induced inflammatory mediators.

Airway epithelial cells were shown to drive the differentiation of monocytes into dendritic cells (DCs) with a suppressive phenotype. In this study, we investigated the impact of virus-induced inflammatory mediator production on the development of DCs. Monocyte differentiation into functional DCs, as reflected by the expression of CD11c, CD123, BDCA-4, and DC-SIGN and the capacity to activate T cells, was similar for respiratory syncytial virus (RSV)-infected and mock-infected BEAS-2B and A549 cells. RSV-conditioned culture media resulted in a partially mature DC phenotype, but failed to up-regulate CD80, CD83, CD86, and CCR7, and failed to release proinflammatory mediators upon Toll-like receptor (TLR) triggering. Nevertheless, these DCs were able to maintain an antiviral response by the release of Type I IFN. Collectively, these data indicate that the airway epithelium maintains an important suppressive DC phenotype under the inflammatory conditions induced by infection with RSV.

Productive efficiency and regulatory reform: The case of vehicle inspection services

Measuring productive efficiency provides information on the likely effects of regulatory reform. We present a Data Envelopment Analysis (DEA) of a sample of 38 vehicle inspection units under a concession regime, between the years 2000 and 2004. The differences in efficiency scores show the potential technical efficiency benefit of introducing some form of incentive regulation or of progressing towards liberalization. We also compute scale efficiency scores, showing that only units in territories with very low population density operate at a sub-optimal scale. Among those that operate at an optimal scale, there are significant differences in size; the largest ones operate in territories with the highest population density. This suggests that the introduction of new units in the most densely populated territories (a likely effect of some form of liberalization) would not be detrimental in terms of scale efficiency. We also find that inspection units belonging to a large, diversified firm show higher technical efficiency, reflecting economies of scale or scope at the firm level. Finally, we show that between 2002 and 2004, a period of high regulatory uncertainty in the sample’s region, technical change was almost zero. Regulatory reform should take due account of scale and diversification effects, while at the same time avoiding regulatory uncertainty.

Transplantation tolerance induced by regulatory T cells: in vivo mechanisms and sites of action.

The mechanisms by which CD4(+)CD25(+)Foxp3(+) T (Treg) cells regulate effector T cells in a transplantation setting and their in vivo homeostasis still remain to be clarified. Using a mouse adoptive transfer model, we analyzed the in vivo expansion, trafficking, and effector function of alloreactive T cells and donor-specific Treg cells, in response to a full-thickness skin allograft. Fluorescent-labeled CD4(+)CD25(-) and antigen-specific Treg cells were transferred alone or co-injected into syngeneic BALB/c-Nude recipients transplanted with skins from (C57BL/6 x BALB/c) F1 donors. Treg cells divided in vivo, migrated and accumulated in the allograft draining lymph nodes as well as within the graft. The co-transfer of Treg cells did not modify the early activation and homing of CD4(+)CD25(-) T cells in secondary lymphoid organs. However, in the presence of Treg cells, alloreactive CD4(+)CD25(-) T cells produced significantly less IFN-gamma and were present in reduced numbers in the secondary lymphoid organs. Furthermore, time-course studies showed that Treg cells were recruited into the allograft at a very early stage after transplantation and effectively prevented the infiltration of effector T cells. In conclusion, suppression of rejection requires the early recruitment to the site of antigenic challenge of donor-specific Treg cells, which then mainly regulate the effector arm of T cell alloresponses.

Methylation profile of TP53 regulatory pathway and mtDNA alterations in breast cancer patients lacking TP53 mutations.

The present study investigated promoter hypermethylation of TP53 regulatory pathways providing a potential link between epigenetic changes and mitochondrial DNA (mtDNA) alterations in breast cancer patients lacking a TP53 mutation. The possibility of using the cancer-specific alterations in serum samples as a blood-based test was also explored. Triple-matched samples (cancerous tissues, matched adjacent normal tissues and serum samples) from breast cancer patients were screened for TP53 mutations, and the promoter methylation profile of P14(ARF), MDM2, TP53 and PTEN genes was analyzed as well as mtDNA alterations, including D-loop mutations and mtDNA content. In the studied cohort, no mutation was found in TP53 (DNA-binding domain). Comparison of P14(ARF) and PTEN methylation patterns showed significant hypermethylation levels in tumor tissues (P < 0.05 and <0.01, respectively) whereas the TP53 tumor suppressor gene was not hypermethylated (P < 0.511). The proportion of PTEN methylation was significantly higher in serum than in the normal tissues and it has a significant correlation to tumor tissues (P < 0.05). mtDNA analysis revealed 36.36% somatic and 90.91% germline mutations in the D-loop region and also significant mtDNA depletion in tumor tissues (P < 0.01). In addition, the mtDNA content in matched serum was significantly lower than in the normal tissues (P < 0.05). These data can provide an insight into the management of a therapeutic approach based on the reversal of epigenetic silencing of the crucial genes involved in regulatory pathways of the tumor suppressor TP53. Additionally, release of significant aberrant methylated PTEN in matched serum samples might represent a promising biomarker for breast cancer.

Authority relationships between obedience and disobedience

Recent episodes of public dissent (such as the demonstrations against G8 policies) raise the issue of the psychological processes triggered in obeying and disobeying the authority. Even if obedience to authority is an important aspect of social life and it plays a key role in maintaining social order, the concept of obedience has been studied in social psychology mainly in terms of its destructive aspects. Besides, most of the studies have overlooked the role of disobedience in the authority relationship. Disobedience may be conceived of as a protest that undermines the legitimacy of the authority or it can represent an instrument for controlling the legitimacy of the authority's demands, becoming a factor protecting against authoritarianism. In this article, a new perspective on the study of the relationship between the individual and the authority is put forward, considering obedience and disobedience as parallel concepts, each having constructive and destructive aspects. 2008 Elsevier Ltd. All rights reserved.

Caught Between Theory and Practice: Government, Market, and Regulatory Failure in Electricity Sector Reforms

The world-wide electricity sector reforms of the early 1990s have revealed the considerable complexities of making market driven reforms in network and infrastructure industries. This paper reflects on the experiences to date with the process and outcomes of marketbased electricity reforms across less-developed, transition and developed economies. The reforms outcomes suggest similar problems facing the electricity sector of these countries though their contexts vary significantly. Many developing and developed economies continue to have investment inadequacy concerns and the need to balance economy efficiency, sustainability and social equity after more than two decades of experience with reforms. We also use a case study of selected countries that in many respects represent the current state of the reform though they are rarely examined. Nepal, Belarus and Ireland are chosen as country-specific case studies for this purpose. We conclude that the changing dynamics of the electricity supply industry (ESI) and policy objectives imply that analysing the success and failure of reforms will indeed remain a complex process.

Factors Affecting Audit Quality in the 2007 UK Regulatory Environment: Perceptions of Chief Financial Officers, Audit Committee Chairs and Audit Engagement Partners

In line with global changes, the UK regulatory regime for audit and corporate governance has changed significantly since the Enron scandal, with an increased role for audit committees and independent inspection of audit firms. UK listed company chief financial officers (CFOs), audit committee chairs (ACCs) and audit partners (APs) were surveyed in 2007 to obtain views on the impact of 36 economic and regulatory factors on audit quality. 498 usable responses were received, representing a response rate of 36%. All groups rated various audit committee interactions with auditors among the factors most enhancing audit quality. Exploratory factor analysis reduces the 36 factors to nine uncorrelated dimensions. In order of extraction, these are: economic risk; audit committee activities; risk of regulatory action; audit firm ethics; economic independence of auditor; audit partner rotation; risk of client loss; audit firm size; and, lastly, International Standards on Auditing (ISAs) and audit inspection. In addition to the activities of the audit committee, risk factors for the auditor (both economic and certain regulatory risks) are believed to most enhance audit quality. However, ISAs and the audit inspection regime, aspects of the ‘standards-surveillance compliance’ regulatory system, are viewed as less effective. Respondents commented that aspects of the changed regime are largely process and compliance driven, with high costs for limited benefits, supporting psychological bias regulation theory that claims there is overconfidence that a useful regulatory intervention exists.

La participation des consommateurs à la construction de l'autorité des normes internationales : vers une économie politique internationale de la traduction

Cette thèse explore les implications politiques de la montée en puissance des normes internationales sur nos sociétés contemporaines et pose la problématique des dynamiques participatives des représentants des consommateurs au sein des formes de pouvoir non étatique à l'aide du cas de l'Organisation internationale de normalisation (ISO). Le renforcement du pouvoir des normes internationales et autres spécifications techniques soulève d'importants enjeux démocratiques qui portent aussi bien sur la représentativité des acteurs qui les élaborent, sur l'articulation des prérogatives publiques et privées dans la gouvernance de la mondialisation, que sur le rôle de l'expertise dans la reconnaissance de ces nouvelles formes de pouvoir. La participation du monde associatif intervient sur ces différents enjeux de manière complexe. Cette recherche s'inscrit à la suite des études en relations internationales/économie politique internationale sur les formes d'autorité non étatique et s'inspire du concept de traduction issu de la sociologie des sciences et techniques pour mettre en lumière le rôle des spécifications techniques dans la construction d'une société de consommation centrée sur la liberté de choix et la façon dont les associations de consommateurs se saisissent des arènes de normalisation pour y faire valoir des préoccupations collectives, leur expertise et leur identité. Cette thèse défend l'idée que les consommateurs participent à la construction de l'autorité des normes internationales par leur rôle dans la traduction qui permet de relier les spécifications techniques au fonctionnement des marchés, au cadre réglementaire de la loi et aux préoccupations sociétales. L'analyse repose sur une observation ethnographique des délibérations d'un comité technique de l'ISO, une recherche-­‐action, la réalisation d'entretiens et la consultation de documents d'archives de l'ISO. -- This thesis explores the political significance of the rise of international standards on contemporary societies and questions the participatory dynamics of consumers' representatives within nonstate forms of power, using the case of the International organization for standardization (ISO). The power granted to international standards and other technical specifications raises important democratic issues regarding the representativity of standard-­‐ writers, the public-­‐private relationships involved in this form of governance or the expertise sustaining the recognition of such new forms of power. The participation of civil society associations affect such issues in complex ways. This research relies on international relations/international political economy approaches of nonstate authority and takes inspiration from the concept of translation developed by science and technology studies to highlight the crucial role played by technical specifications in building a consumer society based on the freedom of choice as well as how consumers' associations take stock of standardization arenas to promote collective issues and claim their expertise and identity. This thesis argues that consumers contribute to the construction of the authority of international standards through their role in the translation that links international standards to the market society, the regulatory state as well as to societal preoccupation. The analysis is based on an ethnographic observation of deliberations within an ISO technical committee, a research-­‐action, interviews as well as on the consultation of ISO archives.

Gare aux hybrides : mythes et réalités de la gouvernance de la mondialisation

Hybrid is often used as a default attribute reflecting lack of clear understanding of the influence of new patterns and actors of structural change beyond states, firms and institutions traditionally involved in regulatory practices across nations. The article argues that the notion of hybrid has a distinct relevance for engaging shortcomings of global governance literature. It explores the lessons to be drawn from ancient mythology by highlighting that ontological ambiguity and emotional ambivalence represent core features of hybrid creatures. It then builds upon critical scholarship in global political economy to conceptualise three generic levels of transfers of authority at which situating the hybrid dimension of governance in contemporary capitalism. Following this approach, the concept of hybrid explicates the ambiguity between formal and informal transfers of authority, which in turn provides an insight into the contested nature of the procedures used to reinforce this type of governance practices.

Arenavirus Nucleoprotein Targets Interferon Regulatory Factor-Activating Kinase IKKε.

Arenaviruses perturb innate antiviral defense by blocking induction of type I interferon (IFN) production. Accordingly, the arenavirus nucleoprotein (NP) was shown to block activation and nuclear translocation of interferon regulatory factor 3 (IRF3) in response to virus infection. Here, we sought to identify cellular factors involved in innate antiviral signaling targeted by arenavirus NP. Consistent with previous studies, infection with the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) prevented phosphorylation of IRF3 in response to infection with Sendai virus, a strong inducer of the retinoic acid-inducible gene I (RIG-I)/mitochondrial antiviral signaling (MAVS) pathway of innate antiviral signaling. Using a combination of coimmunoprecipitation and confocal microscopy, we found that LCMV NP associates with the IκB kinase (IKK)-related kinase IKKε but that, rather unexpectedly, LCMV NP did not bind to the closely related TANK-binding kinase 1 (TBK-1). The NP-IKKε interaction was highly conserved among arenaviruses from different clades. In LCMV-infected cells, IKKε colocalized with NP but not with MAVS located on the outer membrane of mitochondria. LCMV NP bound the kinase domain (KD) of IKKε (IKBKE) and blocked its autocatalytic activity and its ability to phosphorylate IRF3, without undergoing phosphorylation. Together, our data identify IKKε as a novel target of arenavirus NP. Engagement of NP seems to sequester IKKε in an inactive complex. Considering the important functions of IKKε in innate antiviral immunity and other cellular processes, the NP-IKKε interaction likely plays a crucial role in arenavirus-host interaction.

The SOCS3-independent expression of IDO2 supports the homeostatic generation of T regulatory cells by human dendritic cells.

Dendritic cells (DCs) are professional APCs that have a role in the initiation of adaptive immune responses and tolerance. Among the tolerogenic mechanisms, the expression of the enzyme IDO1 represents an effective tool to generate T regulatory cells. In humans, different DC subsets express IDO1, but less is known about the IDO1-related enzyme IDO2. In this study, we found a different pattern of expression and regulation between IDO1 and IDO2 in human circulating DCs. At the protein level, IDO1 is expressed only in circulating myeloid DCs (mDCs) and is modulated by PGE2, whereas IDO2 is expressed in both mDCs and plasmacytoid DCs and is not modulated by PGE2. In healthy subjects, IDO1 expression requires the presence of PGE2 and needs continuous transcription and translation, whereas IDO2 expression is constitutive, independent from suppressor of cytokine signaling 3 activity. Conversely, in patients suffering from inflammatory arthritis, circulating DCs express both IDO1 and IDO2. At the functional level, both mDCs and plasmacytoid DCs generate T regulatory cells through an IDO1/IDO2-dependent mechanism. We conclude that, in humans, whereas IDO1 provides an additional mechanism of tolerance induced by proinflammatory mediators, IDO2 is stably expressed in steady-state conditions and may contribute to the homeostatic tolerogenic capacity of DCs.

Balanç de carbó atmosfèric: raó entre les emissions de metà de les vaques i el segrest forestal de CO2

Treball de recerca realitzat per un alumne d'ensenyament secundari i guardonat amb un Premi CIRIT per fomentar l'esperit científic del Jovent l'any 2009. L’objectiu d’aquest treball és determinar la capacitat de segrest de CO2 d’un bosc dels Pirineus, per tal de reduir el seu efecte hivernacle, en relació a l’impacte climàtic que tindrien les emissions de metà de les vaques. La metodologia s’ha basat en estimar la producció de fusta a partir d’inventaris forestals d’un bosc del Pallars Sobirà, i calcular-ne el segrest de CO2. Per altra banda, s’ha estimat bibliogràficament les emissions de metà d’una vaca. A partir de factors de conversió s’ha estimat la superfície de bosc que compensaria l’efecte hivernacle de les emissions de metà d’una vaca durant un any. El valor obtingut és de 0,727 hectàrees de bosc per vaca i any. Amb aquest valor s’ha estimat la superfície de bosc necessària per compensar les emissions de metà de la població de vaques de Catalunya. Aquests resultats són aproximats, donades les diferències en el creixement dels boscos de Catalunya. Aquest estudi dóna una dada comprensible que posa de manifest el concepte de balanç de carboni i els diferents elements que el formen.