Developmental changes in cardiac recovery from anoxia-reoxygenation.

The developing cardiovascular system is known to operate normally in a hypoxic environment. However, the functional and ultrastructural recovery of embryonic/fetal hearts subjected to anoxia lasting as long as hypoxia/ischemia performed in adult animal models remains to be investigated. Isolated spontaneously beating hearts from Hamburger-Hamilton developmental stages 14 (14HH), 20HH, 24HH, and 27HH chick embryos were subjected in vitro to 30 or 60 min of anoxia followed by 60 min of reoxygenation. Morphological alterations and apoptosis were assessed histologically and by transmission electron microscopy. Anoxia provoked an initial tachycardia followed by bradycardia leading to complete cardiac arrest, except for in the youngest heart, which kept beating. Complete atrioventricular block appeared after 9.4 +/- 1.1, 1.7 +/- 0.2, and 1.6 +/- 0.3 min at stages 20HH, 24HH, and 27HH, respectively. At reoxygenation, sinoatrial activity resumed first in the form of irregular bursts, and one-to-one atrioventricular conduction resumed after 8, 17, and 35 min at stages 20HH, 24HH, and 27HH, respectively. Ventricular shortening recovered within 30 min except at stage 27HH. After 60 min of anoxia, stage 27HH hearts did not retrieve their baseline activity. Whatever the stage and anoxia duration, nuclear and mitochondrial swelling observed at the end of anoxia were reversible with no apoptosis. Thus the embryonic heart is able to fully recover from anoxia/reoxygenation although its anoxic tolerance declines with age. Changes in cellular homeostatic mechanisms rather than in energy metabolism may account for these developmental variations.

Using plan analysis in psychotherapeutic case formulation of borderline personality disorder.

A comprehensive understanding of the patient's problems is essential for a constructive therapeutic behaviour, especially in borderline personality disorder (BPD) where difficult interpersonal patterns are persistent. In these circumstances, the use of an integrative case formulation approach such as Plan Analysis, developed by K. Grawe and F. Caspar, can be of help for therapy planning. The focus here is on instrumental relations between behaviours and the hypothetical Plans and motives 'behind' those behaviours. The present qualitative study aimed at setting a prototypical Plan structure for n = 15 patients presenting a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of BPD using Plan Analysis. The first psychotherapeutic session of every outpatient was video-taped and evaluated according to the Plan Analysis procedure. Inter-rater reliability was established between two independent raters and was considered sufficient. The detailed prototypical Plan structure of BPD showed two main tendencies: first, the important presence of support-seeking among these patients and second, the will to be in control and to protect oneself. This study confirms the existence of several core similarities in the functioning of patients with BPD. These findings are in line with earlier studies and expand the latter with the aim of contributing to the understanding of BPD psychopathology. Clinical implications are discussed. Copyright �� 2011 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: Plan Analysis can especially be of help with patients who have difficult interpersonal patterns, as those presenting with BPD. Two tendencies were found within BPD patients: (1) support-seeking and (2) control and self-protecting Plans. Further research using Plan Analysis should focus on the identification and detail of emotions within BPD.

The role of magma rheology during emplacement of the Listino Suite, Adamello Massif, Italy

This thesis studies individual and contextual antecedents of anti-immigrant attitudes by drawing on intergroup threat and contact, social representation, and value theories. As an alternative to previous multilevel research on the topic, it aims to articulate levels of analysis by putting forward a Person x Context Interaction approach. Moreover, rather than focussing exclusively on the impact of a large immigrant proportion, by introducing ideological climates, it develops and examines the normative societal context in which individuals are embedded. The studies largely draw on cross-sectional survey data across Swiss municipalities (Studies 1 to 3) and European countries (Study 4), but are complemented by elite discourses (Study 5) and online collected survey data (Study 6). Study 1 distinguishes between valued and devalued immigrants, thereby shedding light on the impact of immigrant proportion on intergroup contact and threat. Study 2 focuses on the link between immigrant proportion and attitudes towards the Muslim veil by examining its joint impact with conservative ideologies on the individual and municipality level. Aiming to explain threat related to immigrants, the interplay between immigrant proportion and ideological climates is studied across Swiss municipalities (Study 3) and European countries (Study 4). In addition, by adopting a Person x Context Interaction approach, it is investigated whether a context galvanizes individuals already prone to viewing immigrants as threatening, or mobilizes those generally least likely to express prejudice. Finally, to better understand the role political elites play in fuelling ideological climates, the official discourses on the 2011 England riots are analysed (Study 5). With online survey data collected during the riots, it is then shown that once endorsed, threat-eliciting climates are likely to mobilize negative ethnic diversity attitudes in the larger population (Study 6). Overall, this thesis proposes an integrative approach to studying anti-immigrant attitudes and discusses theoretical and methodological implications. - La pr��sente th��se se penche sur les ant��c��dents individuels et contextuels des attitudes n��gatives envers les immigr�� e s, en combinant les th��ories de la menace intergroupe, du contact, des repr��sentations sociales et des valeurs. Elle a plus pr��cis��ment pour but d'articuler diff��rents niveaux d'analyse �� travers une approche insistant sur les interactions entre Individu et Contexte. Ce faisant, elle propose une alternative aux recherches pr��c��dentes sur le th��me, bas��es sur une perspective multiniveau plus �� classique ��. Au lieu de se pencher uniquement sur l'impact de la pr��sence de populations immigr��es dans un lieu donn��, la recherche r��alis��e a par ailleurs d��velopp�� et ��tudi�� le concept de climat id��ologique, �� savoir le contexte normatif au sein duquel les individus sont plong��s au quotidien. Les ��tudes composant cette th��se se basent essentiellement sur des donn��es d'enqu��te de grande ��chelle, r��colt��es dans diverses municipalit��s Suisses (Etudes 1 �� 3) ou divers pays Europ��ens (Etude 4). Elles sont compl��t��es par l'analyse de discours politiques (Etude 5) et de donn��es r��colt��es sur internet (Etude 6). Distinguant entre immigr��-e'S valoris��-e s et d��valoris��-e-s, l'Etude 1 a eu pour but de mettre en lumi��re l'impact de la pr��sence d'immigr�� e s sur le contact et la menace intergroupes. L'Etude 2 a, quant �� elle, examin�� si la pr��sence d'immigr�� e s interagit avec les id��ologies conservatrices, tant au niveau individuel que municipal, pour expliquer les attitudes envers le voile. Dans le m��me ordre id��e, les ��tudes suivantes ont mis en exergue les effets conjoints de la pr��sence d'immigr��-e s et du climat id��ologique au niveau des municipalit��s suisses (Etude 3) ou des pays Europ��ens (Etude 4). En s'int��ressant aux interactions entre Individu et Contexte, ces ��tudes ont en particulier cherch�� �� observer dans quelle mesure ce dernier pouvait galvaniser les attitudes de personnes qui avaient d��j�� tendance �� percevoir les immigr�� e s comme une menace ou, au contraire, mobiliser des individus desquels on n'attendrait pas de telles attitudes. Pour finir, les derni��res ��tudes ont eu pour but de mettre en lumi��re la mani��re dont les ��lites politiques alimentent les climats id��ologiques. Dans ce but, l'Etude 5 a analys�� les discours officiels donn��s pendant les ��meutes qui ont secou�� Londres en 2011, alors que l'Etude 6 a d��montr�� comment le fait d'��tre en accord avec le message de menace v��hicul�� par ces discours avait pouss�� des individus ��galitaires �� exprimer des attitudes n��gatives envers la diversit�� ethnique. Dans l'ensemble, la pr��sente th��se propose donc une approche int��grative d'��tudier les attitudes n��gatives envers les immigr��-e-s, et en discute les implications th��oriques et m��thodologiques.

H��morragie digestive haute: utilit�� des scores pronostiques [Upper gastrointestinal bleeding: usefulness of prognostic scores].

Upper gastrointestinal bleeding is a potentially serious event, usually requiring urgent endoscopic treatment. Better stratification of the risk of complication or death could optimize management and improve patient outcomes, while ensuring adequate resource allocation. Several prognostic scores have been developed, in order to identify high risk patients, who require immediate treatment, and patients at low risk for whom endoscopy may be delayed. An ideal prognostic score should be accurate, simple, reproducible, and prospectively validated in different populations. Published scores meet these requirements only partially, and thus can only be used as part of an integrative diagnostic and therapeutic process.

GSVA: gene set variation analysis for microarray and RNA-seq data

Gene set enrichment (GSE) analysis is a popular framework for condensing information from gene expression pro���les into a pathway or signature summary. The strengths of this approach over single gene analysis include noise and dimension reduction, as well as greater biological interpretability. As molecular pro���ling experiments move beyond simple case-control studies, robust and ���exible GSE methodologies are needed that can model pathway activity within highly heterogeneous data sets. To address this challenge, we introduce Gene Set Variation Analysis (GSVA), a GSE method that estimates variation of pathway activity over a sample population in an unsupervised manner. We demonstrate the robustness of GSVA in a comparison with current state of the art sample-wise enrichment methods. Further, we provide examples of its utility in di���erential pathway activity and survival analysis. Lastly, we show how GSVA works analogously with data from both microarray and RNA-seq experiments. GSVA provides increased power to detect subtle pathway activity changes over a sample population in comparison to corresponding methods. While GSE methods are generally regarded as end points of a bioinformatic analysis, GSVA constitutes a starting point to build pathway-centric models of biology. Moreover, GSVA contributes to the current need of GSE methods for RNA-seq data. GSVA is an open source software package for R which forms part of the Bioconductor project and can be downloaded at http://www.bioconductor.org.

G��nere i sexoafectivitat segons els adolescents dels usuaris dels centres oberts de la ciutat de Girona

L���objectiu d���aquest treball ��s con��ixer la percepci�� que tenen els adolescents usuaris dels centres oberts de la ciutat de Girona sobre la sexualitat, l���afectivitat, quins rols de g��nere se���n deriven i quines creences els sustenten. El disseny del treball ha estat qualitatiu, observacional, grups de discussi��. Pel que fa als subjectes i al m��tode, la poblaci�� seleccionada ha estat de 33 adolescents i joves d���edats compreses entre els 12 i els 22 anys, usuaris de quatre centres oberts de Girona: el centre obert de Taial��, el Centre Obert de Font de la P��lvora (Onyar), el Centre Obert de Santa Eug��nia i el Centre Obert del Barri Vell. Es van dur a terme grups de discussi�� d���una hora de duraci�� sense descans amb d���entre 6 i 8 persones a partir d���un gui�� format per diversos mites i frases en relaci�� a diversos temes (El festeig, la virginitat, la curiositat pel cos i per la sexualitat, els anticonceptius i les principals fonts d���informaci��) sobre les que havien de dir si estaven d���acord o no i qui creien que les deia (si un noi o una noia). Sobre els resultats del treball cal dir que s���ha observat la persist��ncia d���algunes creences del model del amor rom��ntic en relaci�� al rols de g��nere com la definici�� de la dona vinculada a papers de cura i prevenci��, una dona que t�� acc��s a la sexualitat per�� segueix estan catalogada per la viv��ncia d���aquesta essent una persona ���respectable��� o una ���puta���, que pren un rol m��s actiu en la iniciativa per�� no el l���assertivitat en les relacions; i un home, m��s impulsiu i sexual. En relaci�� als comportaments sexuals destacar l���embar��s no desitjat com la principal preocupaci�� de les relacions i el desconeixement/confusi�� entre els m��todes anticonceptius i de barrera disponibles a la xarxa de salut. Apareix la pornografia com a model emergent de relacions sexuals i models de relaci�� entre homes i dones, en contraposici�� a altres fonts de informaci�� i consulta tradicionals com els amics que segueixen essent la m��s significativa, la fam��lia, els serveis socials i educatius, i Internet. Com a conclusi�� cal dir que queda palesa la necessitat de incorporar una perspectiva de g��nere en la formaci�� curricular dels joves i el fet de seguir replantejant les millors estrat��gies d���intervenci�� per una concepci�� integradora de la sexualitat

Extrasynaptic neurotransmission in the modulation of brain function. Focus on the striatal neuronal glial networks

Extrasynaptic neurotransmission is an important short distance form of volume transmission (VT) and describes the extracellular diffusion of transmitters and modulators after synaptic spillover or extrasynaptic release in the local circuit regions binding to and activating mainly extrasynaptic neuronal and glial receptors in the neuroglial networks of the brain. Receptor-receptor interactions in G protein-coupled receptor (GPCR) heteromers play a major role, on dendritic spines and nerve terminals including glutamate synapses, in the integrative processes of the extrasynaptic signaling. Heteromeric complexes between GPCR and ion-channel receptors play a special role in the integration of the synaptic and extrasynaptic signals. Changes in extracellular concentrations of the classical synaptic neurotransmitters glutamate and GABA found with microdialysis is likely an expression of the activity of the neuron-astrocyte unit of the brain and can be used as an index of VT-mediated actions of these two neurotransmitters in the brain. Thus, the activity of neurons may be functionally linked to the activity of astrocytes, which may release glutamate and GABA to the extracellular space where extrasynaptic glutamate and GABA receptors do exist. Wiring transmission (WT) and VT are fundamental properties of all neurons of the CNS but the balance between WT and VT varies from one nerve cell population to the other. The focus is on the striatal cellular networks, and the WT and VT and their integration via receptor heteromers are described in the GABA projection neurons, the glutamate, dopamine, 5-hydroxytryptamine (5-HT) and histamine striatal afferents, the cholinergic interneurons, and different types of GABA interneurons. In addition, the role in these networks of VT signaling of the energy-dependent modulator adenosine and of endocannabinoids mainly formed in the striatal projection neurons will be underlined to understand the communication in the striatal cellular networks

The clc element of Pseudomonas sp. strain B13, a genomic island with various catabolic properties.

Pseudomonas sp. strain B13 is a bacterium known to degrade chloroaromatic compounds. The properties to use 3- and 4-chlorocatechol are determined by a self-transferable DNA element, the clc element, which normally resides at two locations in the cell's chromosome. Here we report the complete nucleotide sequence of the clc element, demonstrating the unique catabolic properties while showing its relatedness to genomic islands and integrative and conjugative elements rather than to other known catabolic plasmids. As far as catabolic functions, the clc element harbored, in addition to the genes for chlorocatechol degradation, a complete functional operon for 2-aminophenol degradation and genes for a putative aromatic compound transport protein and for a multicomponent aromatic ring dioxygenase similar to anthranilate hydroxylase. The genes for catabolic functions were inducible under various conditions, suggesting a network of catabolic pathway induction. For about half of the open reading frames (ORFs) on the clc element, no clear functional prediction could be given, although some indications were found for functions that were similar to plasmid conjugation. The region in which these ORFs were situated displayed a high overall conservation of nucleotide sequence and gene order to genomic regions in other recently completed bacterial genomes or to other genomic islands. Most notably, except for two discrete regions, the clc element was almost 100% identical over the whole length to a chromosomal region in Burkholderia xenovorans LB400. This indicates the dynamic evolution of this type of element and the continued transition between elements with a more pathogenic character and those with catabolic properties.

Qualitative modeling identifies IL-11 as a novel regulator in maintaining self-renewal in human pluripotent stem cells.

Pluripotency in human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) is regulated by three transcription factors-OCT3/4, SOX2, and NANOG. To fully exploit the therapeutic potential of these cells it is essential to have a good mechanistic understanding of the maintenance of self-renewal and pluripotency. In this study, we demonstrate a powerful systems biology approach in which we first expand literature-based network encompassing the core regulators of pluripotency by assessing the behavior of genes targeted by perturbation experiments. We focused our attention on highly regulated genes encoding cell surface and secreted proteins as these can be more easily manipulated by the use of inhibitors or recombinant proteins. Qualitative modeling based on combining boolean networks and in silico perturbation experiments were employed to identify novel pluripotency-regulating genes. We validated Interleukin-11 (IL-11) and demonstrate that this cytokine is a novel pluripotency-associated factor capable of supporting self-renewal in the absence of exogenously added bFGF in culture. To date, the various protocols for hESCs maintenance require supplementation with bFGF to activate the Activin/Nodal branch of the TGFβ signaling pathway. Additional evidence supporting our findings is that IL-11 belongs to the same protein family as LIF, which is known to be necessary for maintaining pluripotency in mouse but not in human ESCs. These cytokines operate through the same gp130 receptor which interacts with Janus kinases. Our finding might explain why mESCs are in a more na��ve cell state compared to hESCs and how to convert primed hESCs back to the na��ve state. Taken together, our integrative modeling approach has identified novel genes as putative candidates to be incorporated into the expansion of the current gene regulatory network responsible for inducing and maintaining pluripotency.

Verbal labels selectively bias brain responses to high-energy foods.

The influence of external factors on food preferences and choices is poorly understood. Knowing which and how food-external cues impact the sensory processing and cognitive valuation of food would provide a strong benefit toward a more integrative understanding of food intake behavior and potential means of interfering with deviant eating patterns to avoid detrimental health consequences for individuals in the long run. We investigated whether written labels with positive and negative (as opposed to 'neutral') valence differentially modulate the spatio-temporal brain dynamics in response to the subsequent viewing of high- and low-energetic food images. Electrical neuroimaging analyses were applied to visual evoked potentials (VEPs) from 20 normal-weight participants. VEPs and source estimations in response to high- and low- energy foods were differentially affected by the valence of preceding word labels over the ~260-300 ms post-stimulus period. These effects were only observed when high-energy foods were preceded by labels with positive valence. Neural sources in occipital as well as posterior, frontal, insular and cingulate regions were down-regulated. These findings favor cognitive-affective influences especially on the visual responses to high-energetic food cues, potentially indicating decreases in cognitive control and goal-adaptive behavior. Inverse correlations between insular activity and effectiveness in food classification further indicate that this down-regulation directly impacts food-related behavior.

Assimilation des exp��riences probl��matiques: une ��tude de cas de psychoth��rapie psychodynamique limit��e dans le temps [Assimilation of problematic experiences: a case study on short-term dynamic psychotherapy].

The assimilation model is a qualitative and integrative approach that enables to study change processes that occur in psychotherapy. According to Stiles, this model conceives the individual's personality as constituent of different voices; the concept of voice is used to describe traces left by past experiences. During the psychotherapy, we can observe the progressive integration of the problematic voices into the patient's personality. We applied the assimilation model to a 34-session-long case of an effective short-term dynamic psychotherapy. We've chosen eight sessions we transcribed and analyzed by establishing points of contact between the case and the theory. The results are presented and discussed in terms of the evolution of the main voices in the patient.

Of flies, mice and men: a systematic approach to understanding the early life origins of chronic lung disease.

Despite intensive research efforts, the aetiology of the majority of chronic lung diseases (CLD) in both, children and adults, remains elusive. Current therapeutic options are limited, providing only symptomatic relief, rather than treating the underlying condition, or preventing its development in the first place. Thus, there is a strong and unmet clinical need for the development of both, novel effective therapies and preventative strategies for CLD. Many studies suggest that modifications of prenatal and/or early postnatal lung development will have important implications for future lung function and risk of CLD throughout life. This view represents a fundamental change of current pathophysiological concepts and treatment paradigms, and holds the potential to develop novel preventative and/or therapeutic strategies. However, for the successful development of such approaches, key questions, such as a clear understanding of underlying mechanisms of impaired lung development, the identification and validation of relevant preclinical models to facilitate translational research, and the development of concepts for correction of aberrant development, all need to be solved. Accordingly, a European Science Foundation Exploratory Workshop was held where clinical, translational and basic research scientists from different disciplines met to discuss potential mechanisms of developmental origins of CLD, and to identify major knowledge gaps in order to delineate a roadmap for future integrative research.

Multisensory Integration: Flexible Use of General Operations.

Research into the anatomical substrates and "principles" for integrating inputs from separate sensory surfaces has yielded divergent findings. This suggests that multisensory integration is flexible and context dependent and underlines the need for dynamically adaptive neuronal integration mechanisms. We propose that flexible multisensory integration can be explained by a combination of canonical, population-level integrative operations, such as oscillatory phase resetting and divisive normalization. These canonical operations subsume multisensory integration into a fundamental set of principles as to how the brain integrates all sorts of information, and they are being used proactively and adaptively. We illustrate this proposition by unifying recent findings from different research themes such as timing, behavioral goal, and experience-related differences in integration.

The clc element and related genomic islands in Proteobacteria

Genomic islands are large DNA segments, present in most bacterial genome, that are acquired via horizontal gene transfer and contribute to the rapid bacterial evolution and adaptation of the host cell. Here we focus on the clc element (or ICEclc), a 103‑kb genomic island first discovered in Pseudomonas knackmussii B13, as a model of this diverse group of mobile genetic elements. ICEclc is normally integrated in the host bacterial chromosome but can excise and transfer to a new host by conjugation. In this chapter we review the basic features of ICEclc, the mechanisms of its life‑style as well as evolutionary relationships with other known and unknown elements in a variety of Proteobacteria.

Cardiac hypertrophy, low blood pressure, and low aldosterone levels in mice devoid of the three circadian PAR bZip transcription factors DBP, HLF, and TEF.

The cardiovascular system is under the control of the circadian clock, and disturbed circadian rhythms can induce cardiovascular pathologies. This cyclic regulation is probably brought about by the circadian expression of genes encoding enzymes and regulators involved in cardiovascular functions. We have previously shown that the rhythmic transcription of output genes is, in part, regulated by the clock-controlled PAR bZip transcription factors DBP (albumin D-element Binding Protein), HLF (Hepatic Leukemia Factor), and TEF (Thyrotroph Embryonic Factor). The simultaneous deletion of all three PAR bZip transcription factors leads to increased morbidity and shortened life span. Here, we demonstrate that Dbp/Tef/Hlf triple knockout mice develop cardiac hypertrophy and left ventricular dysfunction associated with a low blood pressure. These dysfunctions are exacerbated by an abnormal response to this low blood pressure characterized by low aldosterone levels. The phenotype of PAR bZip knockout mice highlights the importance of circadian regulators in the modulation of cardiovascular functions.