Characterization of NALP2 and NALP3 IL-1β processing inflammasomes

Résumé II y a cinq ans, la découverte d'un nouveau domaine, le PYD domaine, lié aux domaines de la mort, a permis la description de la nouvelle famille des NALP protéines. L'analyse structurelle de cette famille de protéines révéla la présence de deux autres domaines, impliqués dans l'oligomerisation, NACHT, et la détection des ligands, Leucine rich repeats ou LRR. Cette architecture protéique est homologue à celle qui est décrite pour les NODs, les Tol1 récepteurs et tes protéines de résistance chez les plantes. Cette homologie suggère une possible implication des NALPs dans la régulation de l'immunité innée. Premièrement, nous avons décrit les composants minimaux qui permettent à l'inflammasomeNALP3 d'activer la caspase pro-inflammatoire, caspase-1. En comparaison à NALP1, NALP3 ne contient pas de FIIND domaine, ni de CARD domaine en C-terminus et n'interagit pas avec caspase-5. Nous avons découvert une protéine très homologue au C-terminus de NALP1, Cardinal, qui se lie au NACHT domaine de NALP2 et NALP3 par l'intermédiaire de son FIIND domaine. Cardinal possède la capacité d'interagir avec caspase-l, mais seul ASC semble être nécessaire à la maturation de la prointerleukine-1β suite à la stimulation de NALP3. Deuxièmement, notre étude s'est concentrée sur la nature du stimulus capable d'induire la formation et l'activation de l'inflammasome-NALP3. Nous avons démontré que l'ajout de muramyl dipeptide (MDP), produit à partir de la digestion enzymatique de peptidoglycaris bactériens, induit à la fois l'expression de la proIL-1β par la voie NOD2 et sa maturation en IL-1β active par la voie NALP3. Bien que le MDP active l'inflammasome-NALP3, il est incapable d'induire la sécrétion de l'IL-1β mature dans la lignée cellulaire THP1, comparé aux monocytes primaires humains. Cette différence pourrait être liée à l'absence, dans les THP1, de la protéine Filamin, qui est proposée d'interagir avec Cardinal. L'implication de NALP3 dans la maturation de l'IL-lb est confirmée suite à la découverte de mutations sur le gène CIAS1/NALP3/cryopyrin associées à trois maladies auto-inflammatoires : le syndrome de Muckle-Wells (MWS), l'urticaire familial au froid (FCU) et le syndrome CINCA/NOMID. Une élévation constitutive de la maturation et de la sécrétion de la proIL-1β en absence de stimulation MDP est détectée dans les macrophages des patients Muckle-Wells. En conclusion, nos études ont démontré que l'inflammasome-NALP3 doit être finement régulé pour éviter une activité incontrôlée qui représente la base moléculaire des symptômes associés aux syndromes auto-inflammatoires liés à NALP3. Summary Five years ago, the description of the NALP family originated from the discovery of a new death-domain fold family, the PYD domain. NALP contains aprotein-protein interaction domain (PYD), an oligomerization domain (NACHT) and a ligand-sensing domain, leucine rich repeats or LRR. This protein architecture shares similarity with receptors involved in immunity, such as NODS, Toll receptors (TLRs) and related plant resistance proteins, and points to an important role of NALPs in defense mechanisms. We first described the minimal complex involved in the pro-inflammatory Interleukin-1beta (IL-1β) cytokine maturation, called the inflammasome, which contains NALP3. In contrast to NALP1, NALP3, like other members of the NALP family, is devoid of C-terminal FIIND and CARD domains and does not interact with the pro-inflammatory caspase-5. Interestingly, a homolog of the C-terminal portion of NALP1 was found in the human genome and was named Cardinal. We found that NALP2 and NALP3 interact with the CARD-containing proteins Cardinal. Cardinal is able to bind to caspase-1 but is not required for IL-1β maturation through NALP3 activation, as demonstrated for the adaptor ASC. Secondly, our study focused on the stimuli involved in the activation of the NALP3 inflammasome. MDP was shown to induce the expression of proIL1β through NOD2 and then the maturation into active IL-1β by activation of the NALP3 inflammasome. However, in the monocytic THP1 cell line, secretion of IL-1β upon MDP stimulation seems to be independent of the inflammasome activation compared to human primary monocytes. This difference might be linked to a Cardinal-interacting protein, filamin. Until now, the role of Cardinal and filamin is still unknown and remains to be elucidated. Finally, mutations in the NALP3/cryopyrin/CIAS1 gene are associated with three autoinflammatory diseases: Muckle-Wells syndrome, familial cold autoinflammatory syndrome, and CINCA. Constitutive, elevated IL-1β maturation and secretion, even in the absence of MDP stimulation, was observed in macrophages from Muckle-Wells patients and confirmed a key role for the NALP3 inflammasome in innate immunity In conclusion, our studies describes the formation of the NALP3 inflammasome and suggests that this complex has to be tightly regulated to avoid an increased deregulated inflammasome activity that is the molecular basis for the symptoms associated with NALP3-dependent autoinflammatory disorders.

Nucleation and growth of metamorphic minerals in contact aureoles

THESIS ABSTRACT Nucleation and growth of metamorphic minerals are the consequence of changing P-T-X-conditions. The thesis presented here focuses on processes governing nucleation and growth of minerals in contact metamorphic environments using a combination of geochemical analytics (chemical-, isotope-, and trace element composition), statistical treatments of spatial data, and numerical models. It is shown, that a combination of textural modeling and stable isotope analysis allows a distinction between several possible reaction paths for olivine growth in a siliceous dolomite contact aureole. It is suggested that olivine forms directly from dolomite and quartz. The formation of olivine from this metastable reaction implies metamorphic crystallization far from equilibrium. As a major consequence, the spatial distribution of metamorphic mineral assemblages in a contact aureole cannot be interpreted as a proxy for the temporal evolution of a single rock specimen, because each rock undergoes a different reaction path, depending on temperature, heating rate, and fluid-infiltration rate. A detailed calcite-dolomite thermometry study was initiated on multiple scales ranging from aureole scale to the size of individual crystals. Quantitative forward models were developed to evaluate the effect of growth zoning, volume diffusion and the formation of submicroscopic exsolution lamellae (<1 µm) on the measured Mg-distribution in individual calcite crystals and compare the modeling results to field data. This study concludes that Mg-distributions in calcite grains of the Ubehebe Peak contact aureole are the consequence of rapid crystal growth in combination with diffusion and exsolution. The crystallization history of a rock is recorded in the chemical composition, the size and the distribution of its minerals. Near the Cima Uzza summit, located in the southern Adamello massif (Italy), contact metamorphic brucite bearing dolomite marbles are exposed as xenoliths surrounded by mafic intrusive rocks. Brucite is formed retrograde pseudomorphing spherical periclase crystals. Crystal size distributions (CSD's) of brucite pseudomorphs are presented for two profiles and combined with geochemistry data and petrological information. Textural analyses are combined with geochemistry data in a qualitative model that describes the formation periclase. As a major outcome, this expands the potential use of CSD's to systems of mineral formation driven by fluid-infiltration. RESUME DE LA THESE La nucléation et la croissance des minéraux métamorphiques sont la conséquence de changements des conditions de pression, température et composition chimique du système (PT-X). Cette thèse s'intéresse aux processus gouvernant la nucléation et la croissance des minéraux au cours d'un épisode de métamorphisme de contact, en utilisant la géochimie analytique (composition chimique, isotopique et en éléments traces), le traitement statistique des données spatiales et la modélisation numérique. Il est montré que la combinaison d'un modèle textural avec des analyses en isotopes stables permet de distinguer plusieurs chemins de réactions possibles conduisant à la croissance de l'olivine dans une auréole de contact riche en Silice et dolomite. Il est suggéré que l'olivine se forme directement à partir de la dolomie et du quartz. Cette réaction métastable de formation de l'olivine implique une cristallisation métamorphique loin de l'équilibre. La principale conséquence est que la distribution spatiale des assemblages de minéraux métamorphiques dans une auréole de contact ne peut pas être considérée comme un témoin de l'évolution temporelle d'un type de roche donné, puisque chaque type de roche suit différents chemins de réactions, en fonction de la température, la vitesse de réchauffement et le taux d'infiltration du fluide. Une étude thermométrique calcite-dolomite détaillée a été réalisée à diverses échelles, depuis l'échelle de l'auréole de contact jusqu'à l'échelle du cristal. Des modèles numériques quantitatifs ont été développés pour évaluer l'effet des zonations de croissance, de la diffusion volumique et de la formation de lamelles d'exsolution submicroscopiques (<1µm) sur la distribution du magnésium mesuré dans des cristaux de calcite individuels. Les résultats de ce modèle ont été comparés ä des échantillons naturels. Cette étude montre que la distribution du Mg dans les grains de calcite de l'auréole de contact de l'Ubehebe Peak (USA) résulte d'une croissance cristalline rapide, associée aux processus de diffusion et d'exsolution. L'histoire de cristallisation d'une roche est enregistrée dans la composition chimique, la taille et la distribution de ses minéraux. Près du sommet Cima Uzza situé au sud du massif d'Adamello (Italie), des marbres dolomitiques à brucite du métamorphisme de contact forment des xénolithes dans une intrusion mafique. La brucite constitue des pseudomorphes rétrogrades du périclase. Les distributions de taille des cristaux (CSD) des pseudomorphes de brucite sont présentées pour deux profiles et sont combinées aux données géochimiques et pétrologiques. Les analyses textorales sont combinées aux données géochimiques dans un modèle qualitatif qui décrit la formation du périclase. Ceci élargit l'utilisation potentielle de la C5D aux systèmes de formation de minéraux controlés par les infiltrations fluides. THESIS ABSTRACT (GENERAL PUBLIC) Rock textures are essentially the result of a complex interaction of nucleation, growth and deformation as a function of changing physical conditions such as pressure and temperature. Igneous and metamorphic textures are especially attractive to study the different mechanisms of texture formation since most of the parameters like pressure-temperature-paths are quite well known for a variety of geological settings. The fact that textures are supposed to record the crystallization history of a rock traditionally allowed them to be used for geothermobarometry or dating. During the last decades the focus of metamorphic petrology changed from a static point of view, i.e. the representation of a texture as one single point in the petrogenetic grid towards a more dynamic view, where multiple metamorphic processes govern the texture formation, including non-equilibrium processes. This thesis tries to advance our understanding on the processes governing nucleation and growth of minerals in contact metamorphic environments and their dynamic interplay by using a combination of geochemical analyses (chemical-, isotope-, and trace element composition), statistical treatments of spatial data and numerical models. In a first part the thesis describes the formation of metamorphic olivine porphyroblast in the Ubehebe Peak contact aureole (USA). It is shown that not the commonly assumed succession of equilibrium reactions along a T-t-path formed the textures present in the rocks today, but rather the presence of a meta-stable reaction is responsible for forming the olivine porphyroblast. Consequently, the spatial distribution of metamorphic minerals within a contact aureole can no longer be regarded as a proxy for the temporal evolution of a single rock sample. Metamorphic peak temperatures for samples of the Ubehebe Peak contact aureole were determined using calcite-dolomite. This geothermometer is based on the temperature-dependent exchange of Mg between calcite and dolomite. The purpose of the second part of this thesis was to explain the interfering systematic scatter of measured Mg-content on different scales and thus to clarify the interpretation of metamorphic temperatures recorded in carbonates. Numerical quantitative forward models are used to evaluate the effect of several processes on the distribution of magnesium in individual calcite crystals and the modeling results were then compared to measured field. Information about the crystallization history is not only recorded in the chemical composition of grains, like isotope composition or mineral zoning. Crystal size distributions (CSD's) provide essential information about the complex interaction of nucleation and growth of minerals. CSD's of brucite pseudomorphs formed retrograde after periclase of the southern Adamello massif (Italy) are presented. A combination of the textural 3D-information with geochemistry data is then used to evaluate reaction kinetics and to constrain the actual reaction mechanism for the formation of periclase. The reaction is shown to be the consequence of the infiltration of a limited amount of a fluid phase at high temperatures. The composition of this fluid phase is in large disequilibrium with the rest of the rock resulting in very fast reaction rates. RESUME DE LA THESE POUR LE GRAND PUBLIC: La texture d'une roche résulte de l'interaction complexe entre les processus de nucléation, croissance et déformation, en fonction des variations de conditions physiques telles que la pression et la température. Les textures ignées et métamorphiques présentent un intérêt particulier pour l'étude des différents mécanismes à l'origine de ces textures, puisque la plupart des paramètres comme les chemin pression-température sont relativement bien contraints dans la plupart des environnements géologiques. Le fait que les textures soient supposées enregistrer l'histoire de cristallisation des roches permet leur utilisation pour la datation et la géothermobarométrie. Durant les dernières décennies, la recherche en pétrologie métamorphique a évolué depuis une visualisation statique, c'est-à-dire qu'une texture donnée correspondait à un point unique de la grille pétrogénétique, jusqu'à une visualisation plus dynamique, où les multiples processus métamorphiques qui gouvernent 1a formation d'une texture incluent des processus hors équilibre. Cette thèse a pour but d'améliorer les connaissances actuelles sur les processus gouvernant la nucléation et la croissance des minéraux lors d'épisodes de métamorphisme de contact et l'interaction dynamique existant entre nucléation et croissance. Pour cela, les analyses géochimiques (compositions chimiques en éléments majeurs et traces et composition isotopique), le traitement statistique des données spatiales et la modélisation numérique ont été combinés. Dans la première partie, cette thèse décrit la formation de porphyroblastes d'olivine métamorphique dans l'auréole de contact de l'Ubehebe Peak (USA). Il est montré que la succession généralement admise des réactions d'équilibre le long d'un chemin T-t ne peut pas expliquer les textures présentes dans les roches aujourd'hui. Cette thèse montre qu'il s'agirait plutôt d'une réaction métastable qui soit responsable de la formation des porphyroblastes d'olivine. En conséquence, la distribution spatiale des minéraux métamorphiques dans l'auréole de contact ne peut plus être interprétée comme le témoin de l'évolution temporelle d'un échantillon unique de roche. Les pics de température des échantillons de l'auréole de contact de l'Ubehebe Peak ont été déterminés grâce au géothermomètre calcite-dolomite. Celui-ci est basé sur l'échange du magnésium entre la calcite et la dolomite, qui est fonction de la température. Le but de la deuxième partie de cette thèse est d'expliquer la dispersion systématique de la composition en magnésium à différentes échelles, et ainsi d'améliorer l'interprétation des températures du métamorphisme enregistrées dans les carbonates. Des modèles numériques quantitatifs ont permis d'évaluer le rôle de différents processus sur la distribution du magnésium dans des cristaux de calcite individuels. Les résultats des modèles ont été comparés aux échantillons naturels. La composition chimique des grains, comme la composition isotopique ou la zonation minérale, n'est pas le seul témoin de l'histoire de la cristallisation. La distribution de la taille des cristaux (CSD) fournit des informations essentielles sur les interactions entre nucléation et croissance des minéraux. La CSD des pseudomorphes de brucite retrograde formés après le périclase dans le sud du massif Adamello (Italie) est présentée dans la troisième partie. La combinaison entre les données textorales en trois dimensions et les données géochimiques a permis d'évaluer les cinétiques de réaction et de contraindre les mécanismes conduisant à la formation du périclase. Cette réaction est présentée comme étant la conséquence de l'infiltration d'une quantité limitée d'une phase fluide à haute température. La composition de cette phase fluide est en grand déséquilibre avec le reste de la roche, ce qui permet des cinétiques de réactions très rapides.

Bilateral dorsal and ventral fiber pathways for the processing of affective prosody identified by probabilistic fiber tracking.

Dorsal and ventral pathways for syntacto-semantic speech processing in the left hemisphere are represented in the dual-stream model of auditory processing. Here we report new findings for the right dorsal and ventral temporo-frontal pathway during processing of affectively intonated speech (i.e. affective prosody) in humans, together with several left hemispheric structural connections, partly resembling those for syntacto-semantic speech processing. We investigated white matter fiber connectivity between regions responding to affective prosody in several subregions of the bilateral superior temporal cortex (secondary and higher-level auditory cortex) and of the inferior frontal cortex (anterior and posterior inferior frontal gyrus). The fiber connectivity was investigated by using probabilistic diffusion tensor based tractography. The results underscore several so far underestimated auditory pathway connections, especially for the processing of affective prosody, such as a right ventral auditory pathway. The results also suggest the existence of a dual-stream processing in the right hemisphere, and a general predominance of the dorsal pathways in both hemispheres underlying the neural processing of affective prosody in an extended temporo-frontal network.

Respiration, metabolic balance, and attention in affective picture processing

The jointly voluntary and involuntary control of respiration, unique among essential physiological processes, the interconnection of breathing with and its influence on the autonomic nervous system, and disease states associated with the interface between psychology and respiration (e.g., anxiety disorders, hyperventilation syndrome, asthma) make the study of the relationship between respiration and emotion both theoretically and clinically of great relevance. However, the respiratory behavior during affective states is not yet completely understood. We studied breathing pattern responses to 13 picture series varying widely in their affective tone in 37 adults (18 men, 19 women, mean age 26). Time and volume parameters were recorded with the LifeShirt system (VivoMetrics Inc., Ventura, California, USA, see image). We also measured end-tidal pCO2 (EtCO2) with a Microcap Handheld Capnograph (Oridion Medical 1987 Ltd., Jerusalem, Israel) to determine if ventilation is in balance with metabolic demands and spontaneous eye-blinking to investigate the link between respiration and attention. At the end of each picture series, the participants reported their subjective feeling in the affective dimensions of pleasantness and arousal. Increasing self-rated arousal was associated with increasing minute ventilation but not with decreases in EtCO2, suggesting that ventilatory changes during picture viewing paralleled variations in metabolic activity. EtCO2 correlated with pleasantness, and eye-blink rate decreased with increasing unpleasantness in line with a negativity bias in attention. Like MV, inspiratory drive (i.e., mean inspiratory flow) increased with arousal. This relationship reflected increases in inspiratory volume rather than shortening of the time parameters. This study confirms that respiratory responses to affective stimuli are organized to a certain degree along the dimensions of pleasantness and arousal. It shows, for the first time, that during picture viewing, ventilatory increases with increasing arousal are in balance with metabolic activity and that inspiratory volume is modulated by arousal. MV emerges as the most reliable respiratory index of self-perceived arousal. Finally, end-tidal pCO2 is slightly lower during processing of negative as compared to positive picture contents, which is proposed to enhance sensory perception and reflect a negativity bias in attention.

The role of proteolytic processing and the stable signal peptide in expression of the Old World arenavirus envelope glycoprotein ectodomain.

Maturation of the arenavirus GP precursor (GPC) involves proteolytic processing by cellular signal peptidase and the proprotein convertase subtilisin kexin isozyme 1 (SKI-1)/site 1 protease (S1P), yielding a tripartite complex comprised of a stable signal peptide (SSP), the receptor-binding GP1, and the fusion-active transmembrane GP2. Here we investigated the roles of SKI-1/S1P processing and SSP in the biosynthesis of the recombinant GP ectodomains of lymphocytic choriomeningitis virus (LCMV) and Lassa virus (LASV). When expressed in mammalian cells, the LCMV and LASV GP ectodomains underwent processing by SKI-1/S1P, followed by dissociation of GP1 from GP2. The GP2 ectodomain spontaneously formed trimers as revealed by chemical cross-linking. The endogenous SSP, known to be crucial for maturation and transport of full-length arenavirus GPC was dispensable for processing and secretion of the soluble GP ectodomain, suggesting a specific role of SSP in the stable prefusion conformation and transport of full-length GPC.

Characterization of the enzyme involved in the processing of big endothelin-1 in human lung epithelial cells.

Biosynthesis of active endothelin-1 (ET-1) implies an enzymatic processing of the inactive precursor Big ET-1 (1-39) into the mature, 21 amino acid peptide. The aim of this study was to characterize in airway and alveolar epithelial cells the enzymes responsible for this activation. BEAS-2B and A549 cells, which both produce ET-1, were studied in vitro as models for bronchiolar and alveolar cells, respectively. Both cell lines were able to convert exogenously added Big ET-1 (0.1 microM) into ET-1, suggesting a cell surface or an extracellular processing. The conversion was inhibited by phosphoramidon in both cell lines with an IC50 approximately 1 microM, but not by thiorphan, a specific inhibitor of neutral endopeptidase 24.11 (NEP). The endogenous production of serum-stimulated BEAS-2B and A549 cells was not inhibited by thiorphan, and phosphoramidon showed inhibition only at high concentration (>100 microM). Western blotting following electrophoresis in reducing conditions demonstrated a protein of MR 110 corresponding to the ECE-1 monomer in both BEAS-2B and A549 cells, as well as in whole lung extracts. By RT-PCR we revealed the mRNA encoding for the ECE-1b and/or -1c subtype, but not ECE-1a, in both cell lines. We conclude that BEAS-2B and A549 cells are able to process either endogenous or exogenous Big ET-1 by ECE-1 and that isoforms 1b and 1c could be involved in this processing with no significant role of NEP.

Accurate memory for object location by individuals with intellectual disability: Absolute spatial tagging instead of configural processing?

Using head-mounted eye tracker material, we assessed spatial recognition abilities (e.g., reaction to object permutation, removal or replacement with a new object) in participants with intellectual disabilities. The "Intellectual Disabilities (ID)" group (n=40) obtained a score totalling a 93.7% success rate, whereas the "Normal Control" group (n=40) scored 55.6% and took longer to fix their attention on the displaced object. The participants with an intellectual disability thus had a more accurate perception of spatial changes than controls. Interestingly, the ID participants were more reactive to object displacement than to removal of the object. In the specific test of novelty detection, however, the scores were similar, the two groups approaching 100% detection. Analysis of the strategies expressed by the ID group revealed that they engaged in more systematic object checking and were more sensitive than the control group to changes in the structure of the environment. Indeed, during the familiarisation phase, the "ID" group explored the collection of objects more slowly, and fixed their gaze for a longer time upon a significantly lower number of fixation points during visual sweeping.

One minute of grief: Emotional processing in short-term dynamic psychotherapy for adjustment disorder.

OBJECTIVE: Depth of emotional processing has shown to be related to outcome across approaches to psychotherapy. Moreover, a specific emotional sequence has been postulated and tested in several studies on experiential psychotherapy (Pascual-Leone & Greenberg, 2007). This process-outcome study aims at reproducing the sequential model of emotional processing in psychodynamic psychotherapy for adjustment disorder and linking these variables with ultimate therapeutic outcome. METHOD: In this study, 32 patients underwent short-term dynamic psychotherapy. On the basis of reliable clinical change statistics, a subgroup (n = 16) presented with good outcome and another subgroup (n = 16) had a poor outcome in the end of treatment. The strongest alliance session of each case was rated using the observer-rated system Classification of Affective Meaning States. Reliability coefficients for the measure were excellent (κ = .82). RESULTS: Using 1 min as the fine-grained unit of analysis, results showed that the experience of fundamentally adaptive grief was more common in the in-session process of patients with good outcome, compared with those with poor outcomes (χ2 = 6.56, p = .01, d = 1.23). This variable alone predicted 19% of the change in depressive symptoms as measured by the Beck Depression Inventory at the end of treatment. Moreover, sequences of the original model were supported and related to outcome. CONCLUSIONS: These results are discussed within the framework of the sequential model of emotional processing and its possible relevance for psychodynamic psychotherapy. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Processing of the circumsporozoite protein in infected hepatocytes is not dependent on aspartic proteases

CD8(+) T cells play a major role in the protective immune response against the liver stage of malaria. It was previously shown that the circumsporozoite protein (CSP) is processed and presented to specific T cells by both traversed and infected hepatocytes, but their respective antigen processing requirements were not completely defined. In the present study, we show that in vitro processing of the Plasmodium berghei CSP by infected mouse primary hepatocytes is exclusively dependent on proteasomes, while aspartic proteases are also needed in the case of traversed hepatocytes

Respiratory responses associated with affective processing of film stimuli

We investigated respiratory responses during film clip viewing and their relation to the affective dimensions of valence and arousal. Seventy-six subjects participated in a study using a between groups design. To begin with, all participants viewed an emotionally neutral film clip. Then, they were presented with one out of four emotional film clips: a positive high-arousal, a positive low-arousal, a negative high-arousal and a negative low-arousal clip. Respiration, skin conductance level, heart rate, corrugator activity and affective judgments were measured. Expiratory time was shorter and inspiratory duty cycle, mean expiratory flow and minute ventilation were larger during the high-arousal clips compared to the low-arousal clips. The pleasantness of the stimuli had no influence on any respiratory measure. These findings confirm the importance of arousal in respiratory responding but also evidence differences in comparison to previous studies using visual and auditory stimuli. [Authors]

Respiration, metabolic balance, and attention in affective picture processing

The respiratory behavior during affective states is not completely understood. We studied breathing pattern responses to picture series in 37 participants. We also measured end-tidal pCO2 (EtCO2) to determine if ventilation is in balance with metabolic demands and spontaneous eye-blinking to investigate the link between respiration and attention. Minute ventilation (MV) and inspiratory drive increased with self-rated arousal. These relationships reflected increases in inspiratory volume rather than shortening of the time parameters. EtCO2 covaried with pleasantness but not arousal. Eye-blink rate decreased with increasing unpleasantness in line with a negativity bias in attention. This study confirms that respiratory responses to affective stimuli are organized to a certain degree along the dimensions of valence and arousal. It shows, for the first time, that during picture viewing, ventilatory increases with increasing arousal are in balance with metabolic activity and that inspiratory volume is modulated by arousal. MV emerges as the most reliable respiratory index of self-perceived arousal

Visuo-spatial processing in a dynamic and a static working memory paradigm in schizophrenia.

Recent findings suggest that the visuo-spatial sketchpad (VSSP) may be divided into two sub-components processing dynamic or static visual information. This model may be useful to elucidate the confusion of data concerning the functioning of the VSSP in schizophrenia. The present study examined patients with schizophrenia and matched controls in a new working memory paradigm involving dynamic (the Ball Flight Task - BFT) or static (the Static Pattern Task - SPT) visual stimuli. In the BFT, the responses of the patients were apparently based on the retention of the last set of segments of the perceived trajectory, whereas control subjects relied on a more global strategy. We assume that the patients' performances are the result of a reduced capacity in chunking visual information since they relied mainly on the retention of the last set of segments. This assumption is confirmed by the poor performance of the patients in the static task (SPT), which requires a combination of stimulus components into object representations. We assume that the static/dynamic distinction may help us to understand the VSSP deficits in schizophrenia. This distinction also raises questions about the hypothesis that visuo-spatial working memory can simply be dissociated into visual and spatial sub-components.