Distinct levels in Pom1 gradients limit Cdr2 activity and localization to time and position division.

Where and when cells divide are fundamental questions. In rod-shaped fission yeast cells, the DYRK-family kinase Pom1 is organized in concentration gradients from cell poles and controls cell division timing and positioning. Pom1 gradients restrict to mid-cell the SAD-like kinase Cdr2, which recruits Mid1/Anillin for medial division. Pom1 also delays mitotic commitment through Cdr2, which inhibits Wee1. Here, we describe quantitatively the distributions of cortical Pom1 and Cdr2. These reveal low profile overlap contrasting with previous whole-cell measurements and Cdr2 levels increase with cell elongation, raising the possibility that Pom1 regulates mitotic commitment by controlling Cdr2 medial levels. However, we show that distinct thresholds of Pom1 activity define the timing and positioning of division. Three conditions-a separation-of-function Pom1 allele, partial downregulation of Pom1 activity, and haploinsufficiency in diploid cells-yield cells that divide early, similar to pom1 deletion, but medially, like wild-type cells. In these cells, Cdr2 is localized correctly at mid-cell. Further, Cdr2 overexpression promotes precocious mitosis only in absence of Pom1. Thus, Pom1 inhibits Cdr2 for mitotic commitment independently of regulating its localization or cortical levels. Indeed, we show Pom1 restricts Cdr2 activity through phosphorylation of a C-terminal self-inhibitory tail. In summary, our results demonstrate that distinct levels in Pom1 gradients delineate a medial Cdr2 domain, for cell division placement, and control its activity, for mitotic commitment.

France's Charter for the Environment : of Presidents, Principles and Environmental Protection

France amended its constitution in 2005 to include a Charter for the Environment. The Charter lays out France's commitment to supporting the right to a 'balanced environment'. This article first traces the Charter's origins to a legacy-building presidential initiative. Jacques Chirac decided to invest in a neglected policy domain in which his own majority had shown little interest. He was obliged to intervene repeatedly in order to bring this project to a successful conclusion. In doing so, he staked out environmental affairs as an area of potential presidential supremacy. Next, the content of the Charter is examined. In this document, French traditions of universalism come together with an international movement for anticipatory environmental protection. This is reflected in the constitutionalisation of the precautionary principle, which emerged as the most controversial part of the Charter. The debates this provoked tended to caricature a risk-management principle whose meaning has been carefully refined to forestall objections. Finally, the Charter's potential efficacy is analysed. The post-Charter record of legislative and judicial activity concerning the environment is meagre, but not wholly inauspicious.

Some of the early events underlying Th2 cell maturation and susceptibility to Leishmania major infection in BALB/c mice.

The first experimental evidence for the development of polarized CD4+ Th1 and Th2 responses in vivo has been obtained using the murine model of infection with Leishmania major, an intracellular parasite of macrophages in their vertebrate host. Genetically determined resistance and susceptibility to infection with this parasite have been clearly demonstrated to result from the development of polarized Th1 and Th2 responses, respectively. Using this model system, the dominant role of cytokines in the induction of polarized CD4+ responses has been validated in vivo. The requisite role of IL-4 in mediating both Th2 differentiation and susceptibility to infection in BALB/c mice has directed interest towards the search for evidence of IL-4 production early after infection and identification of its cellular source. We have been able to demonstrate a burst of IL-4 production in susceptible BALB/c mice within the first day of infection with L. major and could establish that this rapidly produced IL-4 instructed Th2 lineage commitment of subsequently activated CD4+ T cells and stabilized this commitment by downregulating IL-12 Rbeta2 chain expression, resulting in susceptibility to infection. Strikingly, this early IL-4 response to infection resulted from the cognate recognition of a single epitope in a distinctive antigen, LACK, from this complex microorganism by a restricted population of CD4+ T cells that express Vbeta4-Valpha8 T cell receptors.

Which change talk dimensions are associated with subsequent drinking among young men receiving a brief motivational intervention in a non-clinical setting?

Background: Patient change talk (CT) during brief motivational interventions (BMI) has been linked with subsequent changes in drinking in clinical settings but this link has not been clearly established among young people in non-clinical populations. Objective: To determine which of several CT dimensions assessed during an effective BMI delivered in a non-clinical setting to 20-year old men are associated with drinking 6 months later. Methods: Of 125 individuals receiving a face-to-face BMI session (15.8 ± 5.4 minutes), we recorded and coded a subsample of 42 sessions using the Motivational Interviewing Skill Code 2.1. Each patient change talk utterance was categorized as `Reason´, `Ability´, `Desire´, `Need´, `Commitment´, `Taking steps´, or `Other´. Each utterance was graded according to its strength (absolute value from 1 to 3) and direction (i.e. towards (positive sign) or away (negative sign) from change/in favor of status quo). `Ability´, `Desire´, and `Need´ to change (`ADN´) were grouped together since these codes were too scarce to conduct analyses. Mean strength scores over the entire session were computed for each dimension and later dichotomized in towards change (i.e. mean core > 0) and away from change/in favor of status quo. Negative binomial regression models were used to assess the relationship between CT dimensions and drinking 6 months later, adjusting for drinking at baseline. Results: Compared to subjects with a `Taking steps´ score away from change/in favor of status quo, subjects with a positive `Taking steps´ score reported significantly less drinking 6 months later (Incidence Rate Ration [IRR] for drinks per week: 0.56, 95% Confidence Interval [CI] 0.31, 1.00). IRR (95%CI) for subjects with a positive `ADN´ score was 0.58, (0.32, 1.03). For subjects with a positive `Reason´, `Commitment´, and `Other´ scores, IRR (95%CI) were 1.28 (0.77; 2.12) 1.63 (0.85; 3.14) and 1.03 (0.61; 1.72), respectively. Conclusion: A change talk dimension reflecting steps taken towards change (`Taking steps´) is associated with less drinking 6 months later among young men receiving a BMI in a non-clinical setting. Encouraging patients to take steps towa change may be a worthy objective for clinicians and may explain BMI efficacy.

Molecular genetic framework for protophloem formation.

The phloem performs essential systemic functions in tracheophytes, yet little is known about its molecular genetic specification. Here we show that application of the peptide ligand CLAVATA3/EMBRYO SURROUNDING REGION 45 (CLE45) specifically inhibits specification of protophloem in Arabidopsis roots by locking the sieve element precursor cell in its preceding developmental state. CLE45 treatment, as well as viable transgenic expression of a weak CLE45(G6T) variant, interferes not only with commitment to sieve element fate but also with the formative sieve element precursor cell division that creates protophloem and metaphloem cell files. However, the absence of this division appears to be a secondary effect of discontinuous sieve element files and subsequent systemically reduced auxin signaling in the root meristem. In the absence of the formative sieve element precursor cell division, metaphloem identity is seemingly adopted by the normally procambial cell file instead, pointing to possibly independent positional cues for metaphloem formation. The protophloem formation and differentiation defects in brevis radix (brx) and octopus (ops) mutants are similar to those observed in transgenic seedlings with increased CLE45 activity and can be rescued by loss of function of a putative CLE45 receptor, BARELY ANY MERISTEM 3 (BAM3). Conversely, a dominant gain-of-function ops allele or mild OPS dosage increase suppresses brx defects and confers CLE45 resistance. Thus, our data suggest that delicate quantitative interplay between the opposing activities of BAM3-mediated CLE45 signals and OPS-dependent signals determines cellular commitment to protophloem sieve element fate, with OPS acting as a positive, quantitative master regulator of phloem fate.

Mental Causation : Investigating the mind's powers in a natural world

4.6 Summary and Conclusion In this chapter, we have first tried to make precise the distinctions between the concepts of parthood and coincidence and the concepts of causation and causal influence. These distinc-tions had never been made entirely explicit in the debate on mental causation before, despite the fact that they constantly figure in its background. Section 4.2 then demonstrated that the at-tained definitions are both compatible with all the solutions elaborated in chapters 2 and 3 and that they are even of great help in clarifying both what precisely the mentioned accounts are claiming respectively and what their mutual connections are. In sections 4.3. and 4.4, we have then tried to explore two possible solutions to the problem of mental causation that, at least in these particular versions, have not been explicitly defended in the literature. These solutions we dubbed "overdeteiminationism lite" and "plural determinism". We found the accounts both to bear impressive explanatory capabilities and to be vulnerable to far fewer problems than is commonly supposed. We also found out that they have many corresponding aspects and that their theoretical costs stand in a relation of a relative mutual balance. Our final discussion in section 4.5 revealed, however, that overdetenninationism lite should probably be considered the more successful theory. The fact that it needs to endorse the existence of two kinds of causation, although not unproblematic itself, did not appear as a commitment as strong as that of an ontological hierarchy that extends over all time, which at least the broad version of plural determinism was forced to make.

Addressing non-communicable diseases in the Seychelles: towards a comprehensive plan of action.

This article reviews the different steps taken during the past 20 years for the prevention and control of non-communicable diseases (NCDs) in the Seychelles. National surveys revealed high levels of several cardiovascular risk factors and prompted an organized response, starting with the creation of an NCD unit in the Ministry of Health. Information campaigns and nationwide activities raised awareness and rallied increasingly broad and high-level support. Significant policy was developed including comprehensive tobacco legislation and a School Nutrition Policy that bans soft drinks in schools. NCD guidelines were developed and specialized 'NCD nurses' were trained to complement doctors in district health centers. Decreasing smoking prevalence is evidence of success, but the raising so-called diabesity epidemic calls for an integrated multi-sector policy to mould an environment conducive to healthy behaviors. Essential components of these efforts include: effective surveillance mechanisms supplemented by focused research; generating broad interest and consensus; mobilizing leadership and commitment at all levels; involving local and international expertise; building on existing efforts; and seeking integrated, multi-disciplinary and multi-sector approaches.

Isolation of cardiovascular precursor cells from the human fetal heart.

Weakening of cardiac function in patients with heart failure results from a loss of cardiomyocytes in the damaged heart. Cell replacement therapies as a way to induce myocardial regeneration in humans could represent attractive alternatives to classical drug-based approaches. However, a suitable source of precursor cells, which could produce a functional myocardium after transplantation, remains to be identified. In the present study, we isolated cardiovascular precursor cells from ventricles of human fetal hearts at 12 weeks of gestation. These cells expressed Nkx2.5 but not late cardiac markers such as α-actinin and troponin I. In addition, proliferating cells expressed the mesenchymal stem cell markers CD73, CD90, and CD105. Evidence for functional cardiogenic differentiation in vitro was demonstrated by the upregulation of cardiac gene expression as well as the appearance of cells with organized sarcomeric structures. Importantly, differentiated cells presented spontaneous and triggered calcium signals. Differentiation into smooth muscle cells was also detected. In contrast, precursor cells did not produce endothelial cells. The engraftment and differentiation capacity of green fluorescent protein (GFP)-labeled cardiac precursor cells were then tested in vivo after transfer into the heart of immunodeficient severe combined immunodeficient mice. Engrafted human cells were readily detected in the mouse myocardium. These cells retained their cardiac commitment and differentiated into α-actinin-positive cardiomyocytes. Expression of connexin-43 at the interface between GFP-labeled and endogenous cardiomyocytes indicated that precursor-derived cells connected to the mouse myocardium. Together, these results suggest that human ventricular nonmyocyte cells isolated from fetal hearts represent a suitable source of precursors for cell replacement therapies.

Raison et déraison de la loyauté familiale: un cas clinique

Le concept de loyauté appliquée à l'univers de la thérapie familiale est énormément tributaire de la pensée de Boszormenyi-Nagy. Il semble le placer dans un registre humaniste mais immanent. Si on se réfère à son origine étymologique, la loyauté implique l'obligation légale de tenir la parole donnée. Les enfants apprennent tôt à être loyaux. Leurs comportements réparateurs à l'égard des parents, même négligents ou violents, sont considérés comme l'expression d'une loyauté transmise. L'auteur s'interroge sur l'articulation entre une loyauté comme qualité morale du sujet qui choisit de se soumettre à la loi, à la parole donnée et un conditionnement obligé qui contraint le sujet à assumer des comportements « déraisonnables ». Les avancées de la neurobiologie permettent de répondre, tout au moins en partie, à une telle question. The concept of loyalty in the field of the family therapy is in debt to Boszormenyi-Nagy's work. According to his thought, loyalty commitment is the result of a humanistic but immanent believe. Etymologically, loyalty implies legal commitment to fulfill the promise. Children learn in their early years to be loyal. Reparations towards their parents, even if neglecting or violent, are considered the expression of a transmitted loyalty. The author questions the articulation between loyalty as a moral quality of the subject who chooses to accept the law and the given word, and a forced conditioning which brings the subject to adopt "un-reasonable" behaviors. Recent advances in neuroscience enable us to answer this question, at to some extent.

CD8+ T cell development: CD4 to the rescue.

How immature CD4+CD8+ thymocytes become committed to either the CD4 (helper) or CD8 (cytotoxic) lineage is controversial. Genetic ablation of a silencer element in the gene encoding CD4 provides new evidence that CD8 lineage commitment occurs via a stochastic, rather than instructive, mechanism.

THE USEFUL SIDE OF AMBIVALENCE: Ambivalent attitudes can be adaptive and socially valued

En s'inspirant de la littérature récente qui a dépeint l'ambivalence comme étant adaptative et en lien avec des comportements stratégiques, cette thèse examine le versant utile des attitudes ambivalentes. Elle met tout d'abord en évidence que son expression peut-être sciemment contrôlée et mise en avant pour des raisons d'auto-présentation. De plus, elle démontre que les individus peuvent présenter une attitude ambivalente afin de gagner l'approbation sociale sur un objet d'attitude controversé alors que l'inverse a été observé sur des objets consensuels (Première ligne de recherche). Cette thèse a également révélé que l'expression d'attitudes ambivalentes pouvait amener à être valorisé socialement. En effet, contrairement à des attitudes plus tranchées (pro-normatives ou contre-normatives), les attitudes ambivalentes ont été évaluées de façon plus importante sur la dimension de l'utilité sociale (une dimension qui indique la compétence d'autrui ou encore la propension à évoluer dans la hiérarchie sociale). La valorisation de l'ambivalence n'est apparue que sur la dimension de l'utilité sociale et non sur la dimension de la désirabilité sociale (une dimension qui indique la sympathie d'autrui ainsi que la propension à être apprécié socialement). De plus, ce résultat a été observé sur des thèmes controversés et non sur des thèmes consensuels (Seconde ligne de recherche). Dans l'ensemble cette thèse soutient une approche de l'ambivalence comme donnant lieu à des bénéfices. Elle peut également ouvrir la voie à l'étude de l'ambivalence en lien avec la pensée critique. - Drawing on the recent literature that portrayed ambivalence as being adaptive and linked with strategic behaviors, this thesis examines the useful side of ambivalent attitudes. It first revealed that the expression of ambivalent attitudes could be controlled and purposely displayed for self-presentational concerns. Furthermore, it demonstrated that people could put ambivalence forward to gain social approval when expressing it on controversial social issues, whereas the opposite was true on consensual social issues (First line of research). The thesis also revealed that the expression of ambivalent attitudes could lead to be socially valued. Indeed, contrary to clear-cut attitudes (either pro-normative or counter-normative attitudes), ambivalent attitudes have been evaluated the highest on the social utility dimension (a dimension indicating people's competence as well as the extent to which they are likely to climb in social hierarchy). The valorization of ambivalent attitudes only appeared on social utility and not on social desirability (a dimension indicating people's niceness as well as the extent to which they are likely to be socially appreciated). This effect was true on controversial social issues but not on consensual ones (Second line of research). Overall, this thesis provides support for an approach that conceives attitudinal ambivalence as leading to benefits. It also may open avenues for the study of ambivalence in relation with critical thinking.

Constitution, Diversification and Normalisation of a Health Problem: Organising the Fight against AIDS in Switzerland (1984-2005)

The article traces the formation, diversification and normalization of the AIDS cause in Switzerland. Particular emphasis is placed on interactions between the medical field, public authorities and associative space, the latter being understood as the place where individual and collective actors compete to define the cause. The authors argue that the major phases in the structuring of the struggle, the pace of state intervention and the creation of a multi-organizational field, can only be understood if one adopts a 'configurational perspective' attentive to the manner in which, in a given context and under the effect of particular constraints, key actors strategically interact and contribute to transforming their environment and their chances of reaching their goals. This approach takes into account the changing socio-biological characteristics of those who have committed themselves to the cause. In turn, internal movement divisions about how to respond to the epidemic as well as the changing perceptions of the disease have modified the opportunities for commitment, encouraging certain individual kinds of people and excluding others.

Less is more ? The Commission proposal on access to EU documents and the proper limits of transparency

Transparency is now seen as a key tool of democratic governance. The European Union's commitment to transparency is now at the centre of a crucial debate between the Commission and the Parliament on the future of citizen's right of access to information. This article presents the main characteristics of the current regime and questions the pertinence of the proposed changes in light of the international drive at modernising access to information laws and the attempt at identifying the ̳proper limits of transparency'. The questions raised range from the identification of what can be accessed to the definition of exemption and the protection of competing interests.

Travail militant, action collective et rapports de genre

In that paper we propose a gendered approach to social movements and political activism, based on a critical review of the litterature in French and English. In social movements and militantism studies, gender lines of division are most of the time ignored. Social movements are perceived as being « gender neutral ». However, that dimension is a determinant factor of collective action at the macro level of political opportunities and contexts, at the meso level of organisations and their modes of functionning, at the micro level of the logics of individual commitment and the division of militant labor.