Molecular interactions involved in the transactivation of the human T-cell leukemia virus type 1 promoter mediated by Tax and CREB-2 (ATF-4).

The human T-cell leukemia virus type 1 (HTLV-1) Tax protein activates viral transcription through three 21-bp repeats located in the U3 region of the HTLV-1 long terminal repeat and called Tax-responsive elements (TxREs). Each TxRE contains nucleotide sequences corresponding to imperfect cyclic AMP response elements (CRE). In this study, we demonstrate that the bZIP transcriptional factor CREB-2 is able to bind in vitro to the TxREs and that CREB-2 binding to each of the 21-bp motifs is enhanced by Tax. We also demonstrate that Tax can weakly interact with CREB-2 bound to a cellular palindromic CRE motif such as that found in the somatostatin promoter. Mutagenesis of Tax and CREB-2 demonstrates that both N- and C-terminal domains of Tax and the C-terminal region of CREB-2 are required for direct interaction between the two proteins. In addition, the Tax mutant M47, defective for HTLV-1 activation, is unable to form in vitro a ternary complex with CREB-2 and TxRE. In agreement with recent results suggesting that Tax can recruit the coactivator CREB-binding protein (CBP) on the HTLV-1 promoter, we provide evidence that Tax, CREB-2, and CBP are capable of cooperating to stimulate viral transcription. Taken together, our data highlight the major role played by CREB-2 in Tax-mediated transactivation.

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.

CREB-2, a cellular CRE-dependent transcription repressor, functions in association with Tax as an activator of the human T-cell leukemia virus type 1 promoter.

The Tax protein of the human T-cell leukemia virus type 1 (HTLV-1) has been implicated in human T-cell immortalization. The primary function of Tax is to transcriptionally activate the HTLV-1 promoter, but Tax is also known to stimulate expression of cellular genes. It has been reported to associate with several transcription factors, as well as proteins not involved in transcription. To better characterize potential cellular targets of Tax present in infected cells, a Saccharomyces cerevisiae two-hybrid screening was performed with a cDNA library constructed from the HTLV-1-infected MT2 cell line. From this study, we found 158 positive clones representing seven different cDNAs. We focused our attention on the cDNA encoding the transcription factor CREB-2. CREB-2 is an unconventional member of the ATF/CREB family in that it lacks a protein kinase A (PKA) phosphorylation site and has been reported to negatively regulate transcription from the cyclic AMP response element of the human enkephalin promoter. In this study, we demonstrate that CREB-2 cooperates with Tax to enhance viral transcription and that its basic-leucine zipper C-terminal domain is required for both in vitro and in vivo interactions with Tax. Our results confirm that the activation of the HTLV-1 promoter through Tax and factors of the ATF/CREB family is PKA independent.

Progressive Taxes and Firm Births

Tax reform proposals in the spirit of the "flat tax" model typically aim to reduce three parameters: the average tax burden, the progressivity of the tax schedule, and the complexity of the tax code. We explore the implications of changes in these three parameters for entrepreneurial activity, measured by counts of firm births. The Swiss fiscal system offers sufficient intra-national variation in tax codes to allow us to estimate such effects with considerable precision. We find that high average taxes and complicated tax codes depress firm birth rates, while tax progressivity per se promotes firm births. The latter result supports the existence of an insurance effect from progressive corporate income taxes for risk averse entrepreneurs. However, implied elasticities with respect to the level and complexity of corporate taxes are an order of magnitude larger than elasticities with respect to the progressivity of tax schedules.

The Effect of Tax Revenue Budgeting Errors on Fiscal Balance : Evidence from Swiss cantons

This study is an empirical analysis of the impact of direct tax revenue budgeting errors on fiscal deficits. Using panel data from 26 Swiss cantons between 1980 and 2002, we estimate a single equation model on the fiscal balance, as well as a simultaneous equation model on revenue and expenditure. We use new data on budgeted and actual tax revenue to show that underestimating tax revenue significantly reduces fiscal deficits. Furthermore, we show that this effect is channeled through decreased expenditure. The effects of over and underestimation turn out to be symmetric.

Urban environments and situated institutions : everyday governance in west Bengal

How do processes of power shape the urban environment in small Indian cities? On a day-to-day basis, who actually controls access to and the use of environmental resources? How is this done? Answering these questions contributes to our ability to develop a nuanced understanding the urban condition. In order to investigate these questions an actor-oriented approach is developed, drawing on the anthropological literatures on everyday governance and the everyday state. This conceptual framework informs an urban political ecology approach oriented towards everyday practices and the micro-politics of the (re)production of urban socio-natures. This thesis employs a mixed methods approach to qualitative research. Three cases are presented to explore: para (neighbourhood) clubs as governance actors, the governance of the urban pondscape, and the urban political ecology of solid waste management. These case studies serve to highlight how power shapes the (re)production of urban socio-natures through the everyday environmental governance practices of a complex network of governance actors. This work further demonstrates how multiple intersectionalities, including class, caste and access to political and social authority, shape these practices and their outcomes. Finally, the manner in which balances of power, place making and the formation of subject positions may both result from and shape everyday environmental governance practices and their outcomes is explored. This empirical investigation makes a number of contributions to the literature. It has explores the hereto-understudied topics of environmental governance in small cities in India, the urban political ecologies of non-piped water and of solid waste, and the role of clubs as governance actors. It further contributes to conversations within the literature on how to deepen and broaden Urban Political Ecology by engaging with everyday practices, and cases of ordinary, not-openly contested socio-natures. -- Comment les processus de pouvoir influencent-ils l'environnement urbain dans les petites villes indiennes ? Au quotidien, qui contrôle l'accès et l'utilisation des ressources environnementales ? Comment ce contrôle s'exerce-t-il ? Répondre à ces questions contribue au développement d'une compréhension nuancée de la condition urbaine. Afin d'explorer ces questions une approche actor-oriented de la gouvernance quotidienne est développée, faisant appel aux littératures anthropologiques de la gouvernance quotidienne et de l'everyday state. Ce cadre conceptuel établit ainsi une approche d'Urban Political Ecology orientée vers les pratiques quotidiennes et la micro- politique de la (re) production des socio-natures urbaines. Cette thèse emploie des méthodes qualitatives mixtes. Trois cas sont présentés afin d'étudier : les clubs para (quartier) comme acteurs de la gouvernance; la gouvernance de la pondscape urbaine; et l'urban political ecology de la gestion des déchets solides. Ces études de cas permettent de mettre en lumière la façon dont le pouvoir influence la (re)production des socio-natures urbaines par le biais des pratiques quotidiennes de gouvernance environnementale d'un réseau complexe d'acteurs. Ce travail démontre également comment plusieurs intersectionnalités, y compris la classe, la caste et l'accès au pouvoir politique et social, façonnent ces pratiques de gouvernance et leurs produits. Finalement, cette recherche explore la manière dont les équilibres de pouvoir, la fabrication de lieux et la formation de la position du sujet peuvent à la fois résulter de et contribuer à façonner les pratiques quotidiennes de gouvernance environnementale et leurs produits. Cette investigation empirique fait ainsi plusieurs contributions à la littérature. Elle explore les questions jusque-là sous-étudiées de la gouvernance environnementale dans les petites villes en Inde, de l'urban political ecology de l'eau non courante et des déchets solides, ainsi que du rôle des clubs comme acteurs de la gouvernance. Celle-ci contribue également à des débats sur la façon d'approfondir et d'élargir l'urban political ecology en travaillant sur les pratiques quotidiennes, et sur des cas de socio-natures ordinaires, pas ouvertement contestées.

Dial M for Murder: A Case of Passion Killing, Criminal Evidence and Sultanic Power in Medieval India

This paper considers the structures and applications of the criminal judicial system in the Islamic Later Middle Period as it developed in India under the sultans of Delhi (1200-1400 CE). A fundamental issue in crime and punishment is the relationship between sultanic power and religious authority. Particularly at stake in this relationship is the question of who can sanction the highest form of punishment, i.e. the death penalty (siyāsa). Contemporary historians and scholars in the study of religion investigating the relationship between sharīʿa and siyāsa to reveal the extent and limits of sultanic power show a system of governance that allowed for the delegation of authority, particularly in the area of the judiciary, from the sultan down to viziers and judges. Some scholars depict the relationship between the ʿulamāʾ and the sultan as a kind of stand off. The actual dynamics of legal jurisdiction were much more complex. This study proposes a new interpretive framework for understanding the relationship between political power and religious authority through a critical analysis of the criminal judicial system, law, and historical narrative. In particular, I consider a murder case described by Shams al-dīn Sirāj ʿAfīf in one of the most significant histories written in the later Delhi Sultanate, the Tārīkh-i Fīrūzshāhī.

Introduction : la normalisation des services dans la mondialisation

This book examines the role of technical standards in the regulation of services at the international level. It brings together scholarship in international political economy, French regulation theory, and economic sociology in order to discuss the following questions: Which services are most likely to be internationalised and what actors are the most concerned by the phenomenon? What is the relationship between the internationalisation of services and their institutional environment? What is more particularly the role of technical standards in delivering and using services? The introductory chapter presents a comprehensive analysis of cutting edge research on these questions. It argues that technical standards shape new forms of collective action and transnational authority. The chapter suggests some hypotheses for a new research agenda.

Organisation des secours extrahospitaliers lors du sommet 2003 du G8: nouveau concept de poste médical mobile (PMM) [Prehospital medical care organization during the 2003 G8 summit: a new concept of Mobile Medical Squadrons (MMS)].

OBJECTIVE: The occurrence of the 2003 G8 summit in Evian and the threat of major civil riots or even terrorist attacks in the Swiss neighbourhood forced us to imagine a new system of rescue and medical care in case of numerous victims. Previous occurrences of the G8 in Europe or America have demonstrated the need of flexible and mobile structures, able to respond quickly to crowd movements, unlike the usual static structure of rescue systems designed for major accidents. METHODS: We developed a new concept of Mobile Medical Squadrons (MMS) consisting of several vehicles and medical care and rescue human resources. In our concept, each MMS consisted of 3 emergency doctors, 5 paramedics and 9 first-aid workers. They were designed to handle 15 patients, with a large autonomy in terms of rescue, medical care, evacuation and medical authority. The equipment included medical, resuscitation, simple decontamination, evacuation and communication materials. RESULTS: The MMS were dispatched four times during the G8 summit following civil riots. They took care of 12 injured patients. CONCLUSION: The concept of MMS as a reinforcement of the existing rescue and health care resources appears as a new flexible, a modular and useful concept for the medical management of collective prehospital emergency situations. Its use is suggested instead of the traditional static concept of rescue systems designed for major accidents.

Binding free energy differences in a TCR-peptide-MHC complex induced by a peptide mutation: a simulation analysis.

Recognition by the T-cell receptor (TCR) of immunogenic peptides presented by class I major histocompatibility complexes (MHCs) is the determining event in the specific cellular immune response against virus-infected cells or tumor cells. It is of great interest, therefore, to elucidate the molecular principles upon which the selectivity of a TCR is based. These principles can in turn be used to design therapeutic approaches, such as peptide-based immunotherapies of cancer. In this study, free energy simulation methods are used to analyze the binding free energy difference of a particular TCR (A6) for a wild-type peptide (Tax) and a mutant peptide (Tax P6A), both presented in HLA A2. The computed free energy difference is 2.9 kcal/mol, in good agreement with the experimental value. This makes possible the use of the simulation results for obtaining an understanding of the origin of the free energy difference which was not available from the experimental results. A free energy component analysis makes possible the decomposition of the free energy difference between the binding of the wild-type and mutant peptide into its components. Of particular interest is the fact that better solvation of the mutant peptide when bound to the MHC molecule is an important contribution to the greater affinity of the TCR for the latter. The results make possible identification of the residues of the TCR which are important for the selectivity. This provides an understanding of the molecular principles that govern the recognition. The possibility of using free energy simulations in designing peptide derivatives for cancer immunotherapy is briefly discussed.

Interventions présumées des scribes concernant le motif de l'arbre sacré dans le Pentateuque

Abstract: This article deals with several presumed scribal interventions which all concern the sacred tree motif. One finds deliberate changes in the MT, in the Septuagint, in Targum Onkelos and in the Vulgate. The Greek translators of Genesis and Samuel (1-2 Kingdoms) avoided rendering the word אשׁל "tamarisk" by its equivalent μυρίκη, chosing instead the word ἄρουρα "field". Similarly, the Greek translator of Genesis, in the passage of the death of Rebecca's nurse Deborah, passed over the motif of her burial under a grand tree. According to the hypothesis of the present article, all four changes are related to one other; they might be due to the translator's fear to connect the respective texts with traditions and customs concerning the Egyptian god Osiris. On the other side, a scribe of the proto-Massoretic tradition modified the readings mentioning the large tree of Mamre close to Hebron. By changing the noun's number from singular to plural the corrector tried to conceal the existence and importance of the sacred tree in the tradition of Abraham. By contrast, the scribe did not modify texts related to the sacred tree of Shechem. This disparity of treatment may be explained by the fact that, in the view of the Judean scribe, the tree of Shechem would put the Samaritans in a bad light. Finally, the authors of Targum Onkelos and of the Vulgate intervened almost systematically in Pentateuchal texts having the terms אֵלוֹן) אלון or אַלּוֹן ), which always designate a holy tree. The two expressions are rendered by terms referring to plains (Targum Onkelos) or a valley (Vulgate).