Antibiotic susceptibility and molecular epidemiology of Panton-Valentine leukocidin-positive meticillin-resistant Staphylococcus aureus: An international survey

The antibiotic susceptibility and molecular epidemiology of Panton-Valentine leukocidin (PVL)-positive meticillin-resistant Staphylococcus aureus (MRSA) isolates reported from 17 countries in the Americas, Europe and, Australia-Asia were analysed. Among a total of 3236 non-duplicate isolates, the lowest susceptibility was observed to erythromycin in all regions. Susceptibility to ciprofloxacin showed large variation (25%, 75% and 84% in the Americas, Europe and Australia-Asia, respectively). Two vancomycin-intermediate PVL-positive MRSA isolates were reported, one from Hong Kong and the other from The Netherlands. Resistance to trimethoprim/sulfamethoxazole and linezolid was <1%. Among 1798 MRSA isolates from 13 countries that were tested for the requested 10 non-β-lactam antibiotics, 49.4% were multisusceptible. However, multiresistant isolates (resistant to at least three classes of non-β-lactam antibiotics) were reported from all regions. Sequence type 30 (ST30) was reported worldwide, whereas ST80 and ST93 were exclusive to Europe and Australia, respectively. USA300 and related clones (ST8) are progressively replacing the ST80 clone in several European countries. Eight major clusters were discriminated by multilocus variable-number tandem repeat assay (MLVA), showing a certain geographic specificity. PVL-positive MRSA isolates frequently remain multisusceptible to non-β-lactam agents, but multiresistance is already prevalent in all regions. Surveillance of MRSA susceptibility patterns should be monitored to provide clinicians with the most current information regarding changes in resistance patterns.

Multilayered organization of jasmonate signalling in the regulation of root growth.

Physical damage can strongly affect plant growth, reducing the biomass of developing organs situated at a distance from wounds. These effects, previously studied in leaves, require the activation of jasmonate (JA) signalling. Using a novel assay involving repetitive cotyledon wounding in Arabidopsis seedlings, we uncovered a function of JA in suppressing cell division and elongation in roots. Regulatory JA signalling components were then manipulated to delineate their relative impacts on root growth. The new transcription factor mutant myc2-322B was isolated. In vitro transcription assays and whole-plant approaches revealed that myc2-322B is a dosage-dependent gain-of-function mutant that can amplify JA growth responses. Moreover, myc2-322B displayed extreme hypersensitivity to JA that totally suppressed root elongation. The mutation weakly reduced root growth in undamaged plants but, when the upstream negative regulator NINJA was genetically removed, myc2-322B powerfully repressed root growth through its effects on cell division and cell elongation. Furthermore, in a JA-deficient mutant background, ninja1 myc2-322B still repressed root elongation, indicating that it is possible to generate JA-responses in the absence of JA. We show that NINJA forms a broadly expressed regulatory layer that is required to inhibit JA signalling in the apex of roots grown under basal conditions. By contrast, MYC2, MYC3 and MYC4 displayed cell layer-specific localisations and MYC3 and MYC4 were expressed in mutually exclusive regions. In nature, growing roots are likely subjected to constant mechanical stress during soil penetration that could lead to JA production and subsequent detrimental effects on growth. Our data reveal how distinct negative regulatory layers, including both NINJA-dependent and -independent mechanisms, restrain JA responses to allow normal root growth. Mechanistic insights from this work underline the importance of mapping JA signalling components to specific cell types in order to understand and potentially engineer the growth reduction that follows physical damage.

The Swiss reform of the allocation of tasks : The conventions-programs as a new partnership model for vertical cooperation ?

This research examines the impacts of the Swiss reform of the allocation of tasks which was accepted in 2004 and implemented in 2008 to "re-assign" the responsibilities between the federal government and the cantons. The public tasks were redistributed, according to the leading and fundamental principle of subsidiarity. Seven tasks came under exclusive federal responsibility; ten came under the control of the cantons; and twenty-two "common tasks" were allocated to both the Confederation and the cantons. For these common tasks it wasn't possible to separate the management and the implementation. In order to deal with nineteen of them, the reform introduced the conventions-programs (CPs), which are public law contracts signed by the Confederation with each canton. These CPs are generally valid for periods of four years (2008-11, 2012-15 and 2016-19, respectively). The third period is currently being prepared. By using the principal-agent theory I examine how contracts can improve political relations between a principal (Confederation) and an agent (canton). I also provide a first qualitative analysis by examining the impacts of these contracts on the vertical cooperation and on the implication of different actors by focusing my study on five CPs - protection of cultural heritage and conservation of historic monuments, encouragement of the integration of foreigners, economic development, protection against noise and protection of the nature and landscape - applied in five cantons, which represents twenty-five cases studies.

Social trust : a public good?

Combining theories on social trust and social capital with sociopsychological approaches and applying contextual analyses to Swiss and European survey data, this thesis examines under what circumstances generalised trust, often understood as public good, may not benefit everyone, but instead amplify inequality. The empirical investigation focuses on the Swiss context, but considers different scales of analysis. Two broader questions are addressed. First, might generalised trust imply more or less narrow visions of community and solidarity in different contexts? Applying nonlinear principal component analysis to aggregate indicators, Study 1 explores inclusive and exclusive types of social capital in Europe, measured as regional configurations of generalised trust, civic participation and attitudes towards diversity. Study 2 employs multilevel models to examine how generalised trust, as an individual predisposition and an aggregate climate at the level of Swiss cantons, is linked to equality- directed collective action intention versus radical right support. Second, might high-trust climates impact negatively on disadvantaged members of society, precisely because they reflect a normative discourse of social harmony that impedes recognition of inequality? Study 3 compares how climates of generalised trust at the level of Swiss micro-regions and subjective perceptions of neighbourhood cohesion moderate the negative relationship between socio-economic disadvantage and mental health. Overall, demonstrating beneficial, as well as counterintuitive effects of social trust, this thesis proposes a critical and contextualised approach to the sources and dynamics of social cohesion in democratic societies. -- Cette thèse combine des théories sur le capital social et la confiance sociale avec des approches psychosociales et s'appuie sur des analyses contextuelles de données d'enquêtes suisses et européennes, afin d'étudier dans quelles circonstances la confiance généralisée, souvent présentée comme un bien public, pourrait ne pas bénéficier à tout le monde, mais amplifier les inégalités. Les études empiriques, centrées sur le contexte suisse, intègrent différentes échelles d'analyse et investiguent deux questions principales. Premièrement, la confiance généralisée implique-t-elle des visions plus ou moins restrictives de la communauté et de la solidarité selon le contexte? Dans l'étude 1, une analyse à composantes principales non-linéaire sur des indicateurs agrégés permet d'explorer des types de capital social inclusif et exclusif en Europe, mesurés par des configurations régionales de confiance généralisée, de participation civique, et d'attitudes envers la diversité. L'étude 2 utilise des modèles multiniveaux afin d'analyser comment la confiance généralisée, en tant que prédisposition individuelle et climat agrégé au niveau des cantons suisses, est associée à l'intention de participer à des actions collectives en faveur de l'égalité ou, au contraire, à l'intention de voter pour la droite radicale. Deuxièmement, des climats de haute confiance peuvent-ils avoir un impact négatif sur des membres désavantagés de la société, précisément parce qu'ils reflètent un discours normatif d'harmonie sociale qui empêche la reconnaissance des inégalités? L'étude 3 analyse comment des climats de confiance au niveau des micro-régions suisses et la perception subjective de faire partie d'un environnement cohésif modèrent la relation négative entre le désavantage socio-économique et la santé mentale. En démontrant des effets bénéfiques mais aussi contre-intuitifs de la confiance sociale, cette thèse propose une approche critique et contextualisée des sources et dynamiques de la cohésion sociale dans les sociétés démocratiques.

Evolutionary patchwork of an insecticidal toxin shared between plant-associated pseudomonads and the insect pathogens Photorhabdus and Xenorhabdus.

BACKGROUND: Root-colonizing fluorescent pseudomonads are known for their excellent abilities to protect plants against soil-borne fungal pathogens. Some of these bacteria produce an insecticidal toxin (Fit) suggesting that they may exploit insect hosts as a secondary niche. However, the ecological relevance of insect toxicity and the mechanisms driving the evolution of toxin production remain puzzling. RESULTS: Screening a large collection of plant-associated pseudomonads for insecticidal activity and presence of the Fit toxin revealed that Fit is highly indicative of insecticidal activity and predicts that Pseudomonas protegens and P. chlororaphis are exclusive Fit producers. A comparative evolutionary analysis of Fit toxin-producing Pseudomonas including the insect-pathogenic bacteria Photorhabdus and Xenorhadus, which produce the Fit related Mcf toxin, showed that fit genes are part of a dynamic genomic region with substantial presence/absence polymorphism and local variation in GC base composition. The patchy distribution and phylogenetic incongruence of fit genes indicate that the Fit cluster evolved via horizontal transfer, followed by functional integration of vertically transmitted genes, generating a unique Pseudomonas-specific insect toxin cluster. CONCLUSIONS: Our findings suggest that multiple independent evolutionary events led to formation of at least three versions of the Mcf/Fit toxin highlighting the dynamic nature of insect toxin evolution.

Lipid mobilization and gluconeogenesis in plants: Do glyoxylate cycle enzyme activities constitute a real cycle? A hypothesis

Glyoxysomes are specialized peroxisomes present in various plant organs such as germinating cotyledons or senescing leaves. They are the site of beta-oxidation and of the glyoxylate cycle. These consecutive pathways are essential to the maintenance of gluconeogenesis initiated by the degradation of reserve or structural lipids. In contrast to mitochondrial beta-oxidation, which is prevalent in animal cells, glyoxysomal beta-oxidation and the glyoxylate cycle have no direct access to the mitochondrial respiratory chain because of the impermeability of the glyoxysomal membrane to the reduced cofactors. The necessity of NAD(+) regeneration can conceivably be fulfilled by membrane redox chains and/or by transmembrane shuttles. Experimental evidence based on the active metabolic roles of higher plant glyoxysomes and yeast peroxisomes suggests the coexistence of two mechanisms, namely a reductase/peroxidase membrane redox chain and a malate/aspartate shuttle susceptible to transfer electrons to the mitochondrial ATP generating system. Such a model interconnects beta-oxidation, the glyoxylate cycle, the respiratory chain and gluconeogenesis in such a way that glyoxysomal malate dehydrogenase is an essential and exclusive component of beta-oxidation (NAD(+) regeneration). Consequently, the classical view of the glyoxylate cycle is superseded by a tentative reactional scheme deprived of cyclic character.

Dépistage du risque d'allergie et prévention en maternité : enquête des pratiques AllerNaiss [Screening for the risk of allergy and prevention in French maternity units: A survey].

Allergy has been on the rise for half a century and concerns nearly 30% of children; it has now become a real public health problem. The guidelines on prevention of allergy set up by the French Society of Paediatrics (SFP) and the European Society of Paediatric Allergology and Clinical Immunology (ESPACI) are based on screening children at risk through a systematic search of the family history and recommend, for children at risk, exclusive breastfeeding whenever possible or otherwise utilization of hypoallergenic infant formula, which has demonstrated efficacy. The AllerNaiss practice survey assessed the modes of screening and prevention of allergy in French maternity units in 2012. The SFP guidelines are known by 82% of the maternity units that took part in the survey, and the ESPACI guidelines by 55% of them. A screening strategy is in place in 59% of the participating maternity wards, based on local consensus for 36% of them, 13% of the units having a written screening procedure. Screening is based on the search for a history of allergy in first-degree relatives (99%) during pregnancy (51%), in the delivery room (50%), and after delivery (89%). A mode of prevention of the risk of allergy exists in 62% of the maternity units, most often in writing (49%). A hypoallergenic infant formula is prescribed for non-breastfed children in 90% of the units. The survey shows that there is a real need for formalization of allergy risk screening and prevention of allergy in newborns in French maternity units.

HIF-driven SF3B1 induces KHK-C to enforce fructolysis and heart disease.

Fructose is a major component of dietary sugar and its overconsumption exacerbates key pathological features of metabolic syndrome. The central fructose-metabolising enzyme is ketohexokinase (KHK), which exists in two isoforms: KHK-A and KHK-C, generated through mutually exclusive alternative splicing of KHK pre-mRNAs. KHK-C displays superior affinity for fructose compared with KHK-A and is produced primarily in the liver, thus restricting fructose metabolism almost exclusively to this organ. Here we show that myocardial hypoxia actuates fructose metabolism in human and mouse models of pathological cardiac hypertrophy through hypoxia-inducible factor 1α (HIF1α) activation of SF3B1 and SF3B1-mediated splice switching of KHK-A to KHK-C. Heart-specific depletion of SF3B1 or genetic ablation of Khk, but not Khk-A alone, in mice, suppresses pathological stress-induced fructose metabolism, growth and contractile dysfunction, thus defining signalling components and molecular underpinnings of a fructose metabolism regulatory system crucial for pathological growth.

La carrière du médecin africain en Europe : être médecin avec un diplôme africain au Royaume-Uni, en France et en Suisse

En prenant pour objet la migration des médecins d'Afrique vers trois pays d'Europe (Royaume-Uni, France, Suisse), cet article vise à dépasser une approche s'intéressant de manière exclusive aux facteurs de la décision de migrer. Il prend en considération l'ensemble de la carrière du migrant et notamment les modes d'insertion professionnelle dans le pays d'installation. Ce faisant, l'article vise à appréhender ce qu'il y a de commun dans les motifs du choix de partir et ce qu'il y a de profondément différent dans les situations d'arrivée. L'analyse des contextes nationaux étudiés met en évidence l'importance considérable de l'héritage politico-institutionnel du pays d'arrivée quant à la possibilité d'exercer une carrière médicale.

Asymmetrical nature of the Trollius-Chiastocheta interaction: insights into the evolution of nursery pollination systems

The mutualistic versus antagonistic nature of an interaction is defined by costs and benefits of each partner, which may vary depending on the environment. Contrasting with this dynamic view, several pollination interactions are considered as strictly obligate and mutualistic. Here, we focus on the interaction between Trollius europaeus and Chiastocheta flies, considered as a specialized and obligate nursery pollination system - the flies are thought to be exclusive pollinators of the plant and their larvae develop only in T.europaeus fruits. In this system, features such as the globelike flower shape are claimed to have evolved in a coevolutionary context. We examine the specificity of this pollination system and measure traits related to offspring fitness in isolated T.europaeus populations, in some of which Chiastocheta flies have gone extinct. We hypothesize that if this interaction is specific and obligate, the plant should experience dramatic drop in its relative fitness in the absence of Chiastocheta. Contrasting with this hypothesis, T.europaeus populations without flies demonstrate a similar relative fitness to those with the flies present, contradicting the putative obligatory nature of this pollination system. It also agrees with our observation that many other insects also visit and carry pollen among T.europaeus flowers. We propose that the interaction could have evolved through maximization of by-product benefits of the Chiastocheta visits, through the male flower function, and selection on floral traits by the most effective pollinator. We argue this mechanism is also central in the evolution of other nursery pollination systems.

Mir-21-Sox2 Axis Delineates Glioblastoma Subtypes with Prognostic Impact.

UNLABELLED: Glioblastoma (GBM) is the most aggressive human brain tumor. Although several molecular subtypes of GBM are recognized, a robust molecular prognostic marker has yet to be identified. Here, we report that the stemness regulator Sox2 is a new, clinically important target of microRNA-21 (miR-21) in GBM, with implications for prognosis. Using the MiR-21-Sox2 regulatory axis, approximately half of all GBM tumors present in the Cancer Genome Atlas (TCGA) and in-house patient databases can be mathematically classified into high miR-21/low Sox2 (Class A) or low miR-21/high Sox2 (Class B) subtypes. This classification reflects phenotypically and molecularly distinct characteristics and is not captured by existing classifications. Supporting the distinct nature of the subtypes, gene set enrichment analysis of the TCGA dataset predicted that Class A and Class B tumors were significantly involved in immune/inflammatory response and in chromosome organization and nervous system development, respectively. Patients with Class B tumors had longer overall survival than those with Class A tumors. Analysis of both databases indicated that the Class A/Class B classification is a better predictor of patient survival than currently used parameters. Further, manipulation of MiR-21-Sox2 levels in orthotopic mouse models supported the longer survival of the Class B subtype. The MiR-21-Sox2 association was also found in mouse neural stem cells and in the mouse brain at different developmental stages, suggesting a role in normal development. Therefore, this mechanism-based classification suggests the presence of two distinct populations of GBM patients with distinguishable phenotypic characteristics and clinical outcomes. SIGNIFICANCE STATEMENT: Molecular profiling-based classification of glioblastoma (GBM) into four subtypes has substantially increased our understanding of the biology of the disease and has pointed to the heterogeneous nature of GBM. However, this classification is not mechanism based and its prognostic value is limited. Here, we identify a new mechanism in GBM (the miR-21-Sox2 axis) that can classify ∼50% of patients into two subtypes with distinct molecular, radiological, and pathological characteristics. Importantly, this classification can predict patient survival better than the currently used parameters. Further, analysis of the miR-21-Sox2 relationship in mouse neural stem cells and in the mouse brain at different developmental stages indicates that miR-21 and Sox2 are predominantly expressed in mutually exclusive patterns, suggesting a role in normal neural development.

A New Outlook on Mental Illnesses: Glial Involvement Beyond the Glue.

Mental illnesses have long been perceived as the exclusive consequence of abnormalities in neuronal functioning. Until recently, the role of glial cells in the pathophysiology of mental diseases has largely been overlooked. However recently, multiple lines of evidence suggest more diverse and significant functions of glia with behavior-altering effects. The newly ascribed roles of astrocytes, oligodendrocytes and microglia have led to their examination in brain pathology and mental illnesses. Indeed, abnormalities in glial function, structure and density have been observed in postmortem brain studies of subjects diagnosed with mental illnesses. In this review, we discuss the newly identified functions of glia and highlight the findings of glial abnormalities in psychiatric disorders. We discuss these preclinical and clinical findings implicating the involvement of glial cells in mental illnesses with the perspective that these cells may represent a new target for treatment.

Welfare loss with municipal amalgamations and the willingness-to-pay for the municipality name

Functional advantages and drawbacks are commonly mentioned to rationally justify or condemn municipality amalgamations. However, many consolidation projects are resisted by local governments or citizens on the grounds that amalgamation would dampen local identity. A municipality's name change is probably the most visible sign of the loss of community bond experienced by citizens at amalgamation time. This article aims to put a value on this loss by measuring citizen willingness to pay for their city name. This methodological approach innovates upon the literature on municipal amalgamation and place branding by exploiting the versatility of the so-called contingent valuation method (CVM). CVM confronts respondents, in a survey setting, with a hypothetical market in which a characteristic of interest is exchanged. Here the characteristic is the possibility to retain one's city name for an amalgamated jurisdiction. The article presents the estimates provided by a survey conducted in four Swiss cities.

Revenu de base inconditionnel, valeur, domination

L'article propose une défense et légitimation du RBI. Son introduction, montre-t-il, constituerait un changement de paradigme politique : il substituerait à la régulation de plus en plus exclusive des intérêts par le marché, une forme assurant à chacun·e l'assurance des moyens de son intégration sociale. Dans le cadre capitaliste contemporain caractérisé par l'accélération de la substitution du travail mort au travail vivant, il permettrait de libérer l'activité en mettant fin au chantage conditionnant l'accès à l'argent à l'obtention d'un emploi sur le marché du travail. En sorte que le RBI s'avère ainsi, hic et nunc, condition de liberté pour l'immense majorité d'entre nous.

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.