The efficiency of antigen recognition by CD8+ CTL clones is determined by the frequency of serial TCR engagement.

Using H-2Kd-restricted CTL clones, which are specific for a photoreactive derivative of the Plasmodium berghei circumsporozoite peptide PbCS(252-260) (SYIPSAEKI) and permit assessment of TCR-ligand interactions by TCR photoaffinity labeling, we have previously identified several peptide derivative variants for which TCR-ligand binding and the efficiency of Ag recognition deviated by fivefold or more. Here we report that the functional CTL response (cytotoxicity and IFN-gamma production) correlated with the rate of TCR-ligand complex dissociation, but not the avidity of TCR-ligand binding. While peptide antagonists exhibited very rapid TCR-ligand complex dissociation, slightly slower dissociation was observed for strong agonists. Conversely and surprisingly, weak agonists typically displayed slower dissociation than the wild-type agonists. Acceleration of TCR-ligand complex dissociation by blocking CD8 participation in TCR-ligand binding increased the efficiency of Ag recognition in cases where dissociation was slow. In addition, permanent TCR engagement by TCR-ligand photocross-linking completely abolished sustained intracellular calcium mobilization, which is required for T cell activation. These results indicate that the functional CTL response depends on the frequency of serial TCR engagement, which, in turn, is determined by the rate of TCR-ligand complex dissociation.

Le mouvement peut-il guérir? : histoire de l'engagement des médecins français dans l'élaboration de l'éducation physique (1741-1888)

Résumé : Cette recherche doctorale analyse l'engagement des médecins français autour de l'éducation physique entre 1741 et 1888. Basé sur un travail prosopographique d'identification des médecins qui ont participé à l'élaboration de l'éducation physique, ce travail repose sur une mise en dialogue de leurs prises de position respectives. Pour réaliser cette enquête, nous avons compulsé un large corpus de sources primaires, composé des ouvrages consacrés à la gymnastique médicale mais aussi une très large portion de la production d'imprimés touchant à l'anatomie, l'hygiène, la thérapeutique, la physiologie, l'orthopédie, etc. Le corpus contient également des articles des principaux dictionnaires médicaux de la période et des principales revues médicales du XIXe siècle. Avec une approche critique de l'historiographie et à partir de ce corpus, nous avons travaillé dans le cadre de contextes définis pour saisir au plus près les logiques sociales et scientifiques amenant les médecins auprès de l'éducation physique. Trois conjonctures successives structurent l'engagement médical. Entre 1741 et 1817, la thèse retrace l'émergence d'un questionnement ; les années 1817-1847 constituent un « moment orthopédique » dans la formulation de la gymnastique ; et finalement entre 1847 et 1888, on observe une diversification des voies de légitimation médicale des exercices du corps. Ces trois moments de l'histoire des « discours gymniques médicaux » proposent un certain nombre de convergences : la prégnance de l'orthopédie, une certaine concentration autour de la santé des corps féminins, l'inclusion dans un « projet hygiéniste » ; mais aussi des divergences et des singularités : relatives à la progressive structuration en cours du champ médical, à l'implication progressive du politique (surtout après 1845/1850), aux transformations des pathologies/doctrines médicales « dominantes », ainsi qu'à l'importance plus ou moins forte de l'une ou l'autre des facettes de l'éducation physique (militaire, athlétique, « médicinale » ou pédagogique). Le processus est aussi celui de l'expérimentation de la curation de certaines pathologies (scolioses, affections nerveuses), dans des configurations idéologiques/scientifiques marquées par la « dégénération » (XVIIIe siècle), l'anatomie pathologique (début du XIXe siècle) et plus tard la « dégénérescence » et les affections nerveuses (après 1850). Dans le cadre d'une dynamique d'inspiration « foucaldienne », ces recommandations évoluent d'une anatomopolitique - caractérisée par un essor de discours empreints d'anatomie au XVIIIe siècle - vers une biopolitique - caractérisée par l'engagement de l'Etat qui fait de la gymnastique une discipline d'enseignement, pensée à des fins hygiéniques dans la seconde moitié du XIXe - où le processus réside en fait dans une biologisation progressive des recommandations pratiques. Observée à l'aune de la formulation médicale de l'éducation physique, la biopolitique n'est pas réalisée dans la seconde moitié du XVIIIe, elle se compose lentement aux marges de l'institution scolaire et des gymnastiques pédagogico-militaires pour constituer un projet thérapeutique et hygiénique plus construit après 1850. Abstract : This dissertation analyzes French doctor's involvement in debates and initiatives concerning physical education between 1741 and 1888. Based on a prosopographic inventory of those physicians who participated in the development of physical education, it explores the variety of their discourses with respect to the practice of physical exercises. This investigation relies on a large selection of primary sources: works devoted to medical gymnastic, but also medical treatises related to anatomy, hygiene, therapeutics, physiology, orthopedics, etc. The sources also include articles from the major medical dictionaries and journals of the nineteenth century. These documents are used to explore the socio-scientific mechanisms that underlay physicians' commitment to physical education. Three chronological periods structure medical engagement in the area of physical education. Between 1741 and 1817 the thesis traces the emergence of a questioning; the years 1817 to 1847 represent an « orthopedic moment » in the development of gymnastics; finally between 1847 and 1888, one witnesses a diversification of the legitimation process between medicine and gymnastics. These three moments in the history of « medical and gymnastic discourses » offer a number of similarities: the weight of orthopedics, the ongoing focus on the health of the female body, and the association of these discourses with a « hygienic project ». But differences also distinguish these periods as the medical field became more structured and new medical doctrines became dominant, with the increasing involvement of politics (especially after 1850), and with the changing weight of priorities within physical education (military, athletic, « medical » or pedagogic). Medical discourses centered on the curing of certain diseases (scoliosis or nervous disorders) are analyzed within an ideological configuration marked by the idea of « degeneration » (in the eighteenth century), « pathological anatomy » (in the early nineteenth century) and later « dégénérescence » associated with nervous disorders (after 1850). The dissertation draws on Foucault's historical epistemology to understand how medical recommendations evolve from an anatomopolitics - characterized by a surge in anatomical discourses - toward a biopolitics - characterized by the commitment of the State to introduce gymnastics for hygienic purposes into schools in the second half of the nineteenth century. This process reveals a progressive "biologization" of practical recommendations. The medical discourses about physical education show that Foucault's biopolitical power is not achieved in the second half of the eighteenth century, but develops slowly at the margins of the school system and of pedagogical and military gymnastic, becoming a veritable hygienic and therapeutic project only after 1850.

An alternative socio-ecological strategy? International Trade Unions' engagement with climate change

In the context of a global ecological crisis, it is an important move when trade unions turn to environmentalism. Yet, the form that this environmentalism takes is often overlooked. This is especially the case with international trade unions. Based on an empirical study of international trade unions' engagement with the climate change issue, this article argues that international trade unions follow three different (and partially conflicting) strategies. I label these strategies as 'deliberative', 'collaborative growth' and 'socialist', and I examine each in turn. I argue that such analysis is important if we want to identify the potential for transforming the social relations of production that are at the root of the current climate crisis, and for identifying an alternative socio-ecological strategy.

Thy-1-mediated cell-cell contact induces astrocyte migration through the engagement of αVβ3 integrin and syndecan-4.

Cell adhesion to the extracellular matrix proteins occurs through interactions with integrins that bind to Arg-Gly-Asp (RGD) tripeptides, and syndecan-4, which recognizes the heparin-binding domain of other proteins. Both receptors trigger signaling pathways, including those that activate RhoGTPases such as RhoA and Rac1. This sequence of events modulates cell adhesion to the ECM and cell migration. Using a neuron-astrocyte model, we have reported that the neuronal protein Thy-1 engages αVβ3 integrin and syndecan-4 to induce RhoA activation and strong astrocyte adhesion to their underlying substrate. Thus, because cell-cell interactions and strong cell attachment to the matrix are considered antagonistic to cell migration, we hypothesized that Thy-1 stimulation of astrocytes should preclude cell migration. Here, we studied the effect of Thy-1 expressing neurons on astrocyte polarization and migration using a wound-healing assay and immunofluorescence analysis. Signaling molecules involved were studied by affinity precipitation, western blotting and the usage of specific antibodies. Intriguingly, Thy-1 interaction with its two receptors was found to increase astrocyte polarization and migration. The latter events required interactions of these receptors with both the RGD-like sequence and the heparin-binding domain of Thy-1. Additionally, prolonged Thy-1-receptor interactions inhibited RhoA activation while activating FAK, PI3K and Rac1. Therefore, sustained engagement of integrin and syndecan-4 with the neuronal surface protein Thy-1 induces astrocyte migration. Interestingly we identify here, a cell-cell interaction that despite initially inducing strong cell attachment, favors cell migration upon persistent stimulation by engaging the same signaling receptors and molecules as those utilized by the extracellular matrix proteins to stimulate cell movement.

Emotional and neuroendocrine regulation in very preterm and full-term infants at six months of age

Emotional and neuroendocrine regulation have been shown to be associated. However, results are inconsistent. This paper explores the functioning and relationships between these two systems in 54 healthy preterm and 25 full-term born infants at six months of age. Results showed significant differences between very preterm and full-term children in emotional intensity and regulation, as well as in neuroendocrine regulation. No evidence of an association between neuroendocrine and emotional regulations was found. Results suggest a possible delay in the maturation of the neuroendocrine system as well as in emotional regulation in very preterm infants.

Low prevalence of behavioural and emotional problems among Swiss paediatric patients with inflammatory bowel disease.

OBJECTIVES: Whether behavioural and emotional maladjustment is more prevalent in children with inflammatory bowel disease (IBD) than in healthy controls remains controversial. The aim of this study was to assess paediatric IBD patients for problems with emotional and behavioural adjustment and to examine associations with clinical and demographic variables. METHODS: Data from paediatric patients with IBD enrolled in the Swiss IBD Cohort Study and the results of both the parent-rated Strengths and Difficulties Questionnaire (SDQ) and the self-reported Child Depression Inventory (CDI) were analysed. Of the 148 registered patients, 126 had at least one questionnaire completed and were included. RESULTS: The mean age of 71 patients with Crohn's disease (44 males, 27 females) was 13.4 years, and 12.8 years for the 55 patients with ulcerative or indeterminate colitis. The mean duration of disease was 1.2 and 2.7 years, respectively. The total score of the SDQ was abnormal in 11.4% of cases compared to 10% in the normal population. Abnormal sub-scores were found in 20.2% of subjects for the domain of emotional problems and in 17.1% for problems with peers. The total CDI T score indicated a significantly lower prevalence of clinical depression in IBD patients than in normal youth. No correlation between the total SDQ scores or the CDI T scores and gender, type or duration of IBD, inflammatory markers or disease scores was found. CONCLUSIONS: The prevalence of problems with behavioural and emotional adjustment among Swiss paediatric IBD patients is low and comparable to that of the normal population.

Proactive motivation and engagement in career behaviors: Investigating direct, mediated, and moderated effects

Proactive career behaviors become increasingly important in today's career environment, but little is known about how and when motivational patterns affect individual differences. In a six-month longitudinal study among German university students (Study 1; N = 289) it was demonstrated that motivation in terms of "can do" (self-efficacy and context beliefs), "reason to" (autonomous career goals), and "energized to" (positive affect) significantly predicted career behaviors. Contrary to expectation, negative context beliefs had a positive effect when combined with other motivational states. Study 2 replicated and extended those results by investigating whether "can do" motivation mediates the effect of proactive personality and whether those effects are conditional upon the degree of career choice decidedness. We tested a moderated multiple mediation model with a unique sample of 134 German students, assessed three times, each interval being 6 weeks apart. The results showed that effects of proactivity were partially carried through higher self-efficacy beliefs but not context beliefs. Supporting a moderation model, indirect effects through self-efficacy beliefs were not present for students with very low decidedness.

Selective attention to emotional stimuli: What IQ and Openness do, and emotional intelligence does not

We examined how general intelligence, personality, and emotional intelligence-measured as an ability using the MSCEIT-predicted performance on a selective-attention task requiring participants to ignore distracting emotion information. We used a visual prime in which participants saw a pair of faces depicting emotions; their task was to focus on one of the faces (the target) while ignoring the other (the distractor). Next, participants categorized a string of letters (word or nonword), which was either congruent to the target or the distractor. The speed of response to categorizing the string was recorded. Given the emotional nature of the stimuli and the emotional information processing involved in the task, we were surprised to see that none of the MSCEIT branches predicted performance. However, general intelligence and openness to experience reduced response time.

Emotional processing in a ten-session general psychiatric treatment for borderline personality disorder: a case study.

This study examines the effects of a borderline-specific treatment, called general psychiatric management, on emotional change, outcome and therapeutic alliance of an outpatient presenting with borderline personality disorder. Based on the sequential model of emotional processing, emotional states were assessed in a 10-session setting. The case showed an increase in expressions of distress and no change in therapeutic alliance and tended towards general deterioration. Results suggest emotional processing may play a lesser role in general psychiatric management in early phase treatment than previously hypothezised. Copyright © 2015 John Wiley & Sons, Ltd.