The central histaminergic neurons in vitro, and their neuroprotective role in excitotoxic cell death in the postnatal rat hippocampus.

Histamine acts as a neurotransmitter in the central nervous system. Brain histamine in synthesized in neurons located to the posterior hypothalamus, from where these neurons send their projections to different parts of the brain. Released histamine participates in the regulation of several physiological functions such as arousal, attention and body homeostasis. Disturbances in the histaminergic system have been detected in diseases such as epilepsy, sleep disorders, anxiety, depression, Alzheimer’s disease, and schizophrenia. The purpose of this thesis was to develop optimal culture conditions for the histaminergic neurons, to study their detailed morphology, and to find out their significance in the kainic acid (KA)-induced neuronal death in the immature rat hippocampus. The morphology of the histaminergic neurons in vitro was comparable with the earlier findings. Histamine-containing vesicles were found in the axon but also in the cell body and dendrites suggesting a possibility for the somatodendritic release. Moreover, histamine was shown to be colocalized with the vesicular monoamine transporter 2 (VMAT2) suggesting that VMAT2 transports histamine to the subcellular storage vesicles. Furthermore, histamine was localized with γ-aminobutyric acid (GABA) in distinct storage vesicles and with neuropeptide galanin partly in the same storage vesicles suggesting different corelease mechanisms for GABA and galanin with histamine. In the organotypic hippocampal slice cultures, KA-induced neuronal death was first detected 12 h after the treatment being restricted mainly to the CA3 subregion. Moreover, cell death was irreversible, since the 48 h recovery period did not save the cells, but instead increased the damage. Finally, neuronal death was suggested to be necrotic, since intracellular apoptotic pathways were not activated, and the morphological changes detected with the electron microscopy were characteristic for necrosis. In the coculture system of the hippocampal and posterior hypothalamic slices, histaminergic neurons significantly decreased epileptiform burst activity and neuronal death in the hippocampal slices, this effect being mediated by histamine 1 (H1) and 3 (H3) receptors. In conclusion, the histaminergic neurons were maintained succesfully in the in vitro conditions exhibiting comparable morphological characteristics as detected earlier in vivo. Moreover, they developed functional innervations within the hippocampal slices in the coculture system. Finally, the KA-induced regionspecific, irreversible and necrotic hippocampal pyramidal cell damage was significantly decreased by the histaminergic neurons through H1 and H3 receptors.

Gp120/CD4 blocking antibodies are frequently elicited in ART-naïve chronically HIV-1 infected individuals

Antibodies with the ability to block the interaction of HIV-1 envelope glycoprotein (Env) gp120 with CD4, including those overlapping the CD4 binding site (CD4bs antibodies), can protect from infection by HIV-1, and their elicitation may be an interesting goal for any vaccination strategy. To identify gp120/CD4 blocking antibodies in plasma samples from HIV-1 infected individuals we have developed a competitive flow cytometry-based functional assay. In a cohort of treatment-naïve chronically infected patients, we showed that gp120/ CD4 blocking antibodies were frequently elicited (detected in 97% plasma samples) and correlated with binding to trimeric HIV-1 envelope glycoproteins. However, no correlation was observed between functional CD4 binding blockade data and titer of CD4bs antibodies determined by ELISA using resurfaced gp120 proteins. Consistently, plasma samples lacking CD4bs antibodies were able to block the interaction between gp120 and its receptor, indicating that antibodies recognizing other epitopes, such as PGT126 and PG16, can also play the same role. Antibodies blocking CD4 binding increased over time and correlated positively with the capacity of plasma samples to neutralize the laboratory-adapted NL4.3 and BaL virus isolates, suggesting their potential contribution to the neutralizing workforce of plasma in vivo. Determining whether this response can be boosted to achieve broadly neutralizing antibodies may provide valuable information for the design of new strategies aimed to improve the anti-HIV-1 humoral response and to develop a successful HIV- 1 vaccine.

Detection of early apoptosis and cell death in T CD4+ and CD8+ cells from lesions of patients with localized cutaneous leishmaniasis

Human localized cutaneous leishmaniasis (LCL), induced by Leishmania braziliensis, ranges from a clinically mild, self-healing disease with localized cutaneous lesions to severe forms which can present secondary metastatic lesions. The T cell-mediated immune response is extremely important to define the outcome of the disease; however, the underlying mechanisms involved are not fully understood. A flow cytometric analysis of incorporation of 7-amino actinomycin D and CD4+ or CD8+ T cell surface phenotyping was used to determine whether different frequencies of early apoptosis or accidental cell death occur at different stages of LCL lesions. When all cells obtained from a biopsy sample were analyzed, larger numbers of early apoptotic and dead cells were observed in lesions from patients with active disease (mean = 39.5 ± 2.7%) as compared with lesions undergoing spontaneous healing (mean = 17.8 ± 2.2%). Cells displaying normal viability patterns obtained from active LCL lesions showed higher numbers of early apoptotic events among CD8+ than among CD4+ T cells (mean = 28.5 ± 3.8 and 15.3 ± 3.0%, respectively). The higher frequency of cell death events in CD8+ T cells from patients with LCL may be associated with an active form of the disease. In addition, low frequencies of early apoptotic events among the CD8+ T cells were observed in two patients with self-healing lesions. Although the number of patients in the latter group was small, it is possible to speculate that, during the immune response, differences in apoptotic events in CD4+ and CD8+ T cell subsets could be responsible for controlling the CD4/CD8 ratio, thus leading to healing or maintenance of disease.

Cholesterol induces fetal rat enterocyte death in culture

The effect of cholesterol on fetal rat enterocytes and IEC-6 cells (line originated from normal rat small intestine) was examined. Both cells were cultured in the presence of 20 to 80 µM cholesterol for up to 72 h. Apoptosis was determined by flow cytometric analysis and fluorescence microscopy. The expression of HMG-CoA reductase and peroxisome proliferator-activated receptor gamma (PPARgamma) was measured by RT-PCR. The addition of 20 µM cholesterol reduced enterocyte proliferation as early as 6 h of culture. Reduction of enterocyte proliferation by 28 and 41% was observed after 24 h of culture in the presence and absence of 10% fetal calf serum, respectively, with the effect lasting up to 72 h. Treatment of IEC-6 cells with cholesterol for 24 h raised the proportion of cells with fragmented DNA by 9.7% at 40 µM and by 20.8% at 80 µM. When the culture period was extended to 48 h, the effect of cholesterol was still more pronounced, with the percent of cells with fragmented DNA reaching 53.5% for 40 µM and 84.3% for 80 µM. Chromatin condensation of IEC-6 cells was observed after treatment with cholesterol even at 20 µM. Cholesterol did not affect HMG-CoA reductase expression. A dose-dependent increase in PPARgamma expression in fetal rat enterocytes was observed. The expression of PPAR-gamma was raised by 7- and 40-fold, in the presence and absence of fetal calf serum, respectively, with cholesterol at 80 mM. The apoptotic effect of cholesterol on enterocytes was possibly due to an increase in PPARgamma expression.

Utility of a novel risk score for prediction of ventricular tachycardia and cardiac death in chronic Chagas disease - the SEARCH-RIO study

The SEARCH-RIO study prospectively investigated electrocardiogram (ECG)-derived variables in chronic Chagas disease (CCD) as predictors of cardiac death and new onset ventricular tachycardia (VT). Cardiac arrhythmia is a major cause of death in CCD, and electrical markers may play a significant role in risk stratification. One hundred clinically stable outpatients with CCD were enrolled in this study. They initially underwent a 12-lead resting ECG, signal-averaged ECG, and 24-h ambulatory ECG. Abnormal Q-waves, filtered QRS duration, intraventricular electrical transients (IVET), 24-h standard deviation of normal RR intervals (SDNN), and VT were assessed. Echocardiograms assessed left ventricular ejection fraction. Predictors of cardiac death and new onset VT were identified in a Cox proportional hazard model. During a mean follow-up of 95.3 months, 36 patients had adverse events: 22 new onset VT (mean±SD, 18.4±4‰/year) and 20 deaths (26.4±1.8‰/year). In multivariate analysis, only Q-wave (hazard ratio, HR=6.7; P<0.001), VT (HR=5.3; P<0.001), SDNN<100 ms (HR=4.0; P=0.006), and IVET+ (HR=3.0; P=0.04) were independent predictors of the composite endpoint of cardiac death and new onset VT. A prognostic score was developed by weighting points proportional to beta coefficients and summing-up: Q-wave=2; VT=2; SDNN<100 ms=1; IVET+=1. Receiver operating characteristic curve analysis optimized the cutoff value at >1. In 10,000 bootstraps, the C-statistic of this novel score was non-inferior to a previously validated (Rassi) score (0.89±0.03 and 0.80±0.05, respectively; test for non-inferiority: P<0.001). In CCD, surface ECG-derived variables are predictors of cardiac death and new onset VT.

IL-6 and TNF-α serum levels are associated with early death in community-acquired pneumonia patients

Community-acquired pneumonia (CAP) is amongst the leading causes of death worldwide. As inflammatory markers, cytokines can predict outcomes, if interpreted together with clinical data and scoring systems such as CURB-65, CRB, and Acute Physiology and Chronic Health Evaluation II (APACHE II). The aim of this study was to determine the impact of inflammatory biomarkers on the early mortality of hospitalized CAP patients. Twenty-seven CAP patients needing hospitalization were enrolled for the study and samples of interleukin-1 (IL-1) and interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), and homocystein were collected at the time of admission (day 1) as well as on the seventh day of the treatment. There was a significant reduction in the levels of IL-6 between the first and the second collections. Median IL-6 values decreased from 24 pg/mL (day 1) to 8 pg/mL (day 7) (P=0.016). The median levels of TNF-α were higher in patients: i) with acute kidney injury (AKI) (P=0.045), ii) requiring mechanical ventilation (P=0.040), iii) with short hospital stays (P=0.009), iv) admitted to the intensive care unit (ICU) (P=0.040), v) who died early (P=0.003), and vi) with worse CRB scores (P=0.013). In summary, IL-6 and TNF-α levels were associated with early mortality of CAP patients. Longer admission levels demonstrated greater likelihood of early death and overall mortality, necessity of mechanical ventilation, and AKI.

Developmental patterns of individiuals within a sensory-based learning environment in art education : insights emerging from a case study /

My research permitted me to reexamine my recent evaluations of the Leaf Project given to the Foundation Year students during the fall semester of 1997. My personal description of the drawing curriculum formed part of the matrix of the Foundation Core Studies at the Ontario College of Art and Design. Research was based on the random selection of 1 8 students distributed over six of my teaching groups. The entire process included a representation of all grade levels. The intent of the research was to provide a pattern of alternative insights that could provide a more meaningful method of evaluation for visual learners in an art education setting. Visual methods of learning are indeed complex and involve the interplay of many sensory modalities of input. Using a qualitative method of research analysis, a series of queries were proposed into a structured matrix grid for seeking out possible and emerging patterns of learning. The grid provided for interrelated visual and linguistic analysis with emphasis in reflection and interconnectedness. Sensory-based modes of learning are currently being studied and discussed amongst educators as alternative approaches to learning. As patterns emerged from the research, it became apparent that a paradigm for evaluation would have to be a progressive profile of the learning that would take into account many of the different and evolving learning processes of the individual. A broader review of the student's entire development within the Foundation Year Program would have to have a shared evaluation through a cross section of representative faculty in the program. The results from the research were never intended to be conclusive. We realized from the start that sensory-based learning is a difficult process to evaluate from traditional standards used in education. The potential of such a process of inquiry permits the researcher to ask for a set of queries that might provide for a deeper form of evaluation unique to the students and their related learning environment. Only in this context can qualitative methods be used to profile their learning experiences in an expressive and meaningful manner.

Making it "click": collaborative perceptions of creative practice in art education /

Making it "Click": Collaborative Perceptions ofCreative Practice in Art Education examined the teaching practice of 6 art educators who conducted their work through the Niagara Falls Art Gallery's (NFAG) in-schools and Children's Museum programmes. These community resources service the elementary levels of participatory Public, Catholic and French schools in the Niagara Peninsula. The goal of this research was to find ways in which these teachers could explore their creative potential as art educators. The "click," a term introduced by participants indicating the coming together of all positive factors towards creativity, became the central theme behind this study. Research revealed that the effective creative process was not merely a singular phase, but rather a series of 4 processes: 1 , gathering knowledge; 2, intuitive and experiential; 3, the informal presentation of information in which creativity as a process was explored; and 4, formal presentation that took the analysis of information to a deeper, holistic level. To examine the ways in which experience and knowledge could be shared and brought together through a collaborative process, this study employed data collection that used literature research, interviews, focus group discussions, and personal journal entries. Follow-up discussions that assessed the effectiveness of action research, took place VA months after the initial meetings. It is hoped that this study might assist in creative educational practices, for myself as a member of the NFAG teaching team, for colleagues in the art programmes, art educators, and other teachers in the broader disciplines of education.

The ‘Is’ of Fiction Elgin/Goodman Fictionalism : fictions in art and science

Cet essai a pour objet le rôle de la notion de fiction dans les domaines de l’art et de la science. Essentiellement, je soutiens que « fiction » dans ce contexte est « a category mistake » (concept versus genre) et je crois que cet essai peut réussir à « cuire du pain philosophique » en dévoilant une dispute verbale. Je suggère donc de clore un débat philosophique dans son intégralité. Je présente un exposé du style de fictionnalisme abordé par Catherine Z. Elgin et Nelson Goodman (que ce soit dans le contexte des arts ou des sciences, nous parvenons à la compréhension grâce à des fictions sous formes de « vérités non littérales ») et j’explore le concept de la fiction. Je soutiens que les représentations (textes descriptifs de toutes sortes, incluant les modèles) sont constituées d’éléments fictionnels et d’éléments facettés (à l’exception de la version idéale possible ou impossible, c’est-à-dire dans l’esprit de Dieu, qui n’inclurait que les facettes.) La compréhension ne peut provenir de la fiction, mais plutôt d’éléments facettés ordonnés de manière à créer une compréhension qui conduit généralement à des prédictions, des explications et des manipulations. Je définis les facettes comme ayant des caractéristiques organisées, alors que les fictions ont des caractéristiques désorganisées. La fiction dans son intégralité est donc, par définition, l’expression du néant (of nothing), ou en matière de langues idéales (mathématiques), l’expression de contradiction. Les fictions et les facettes relèvent des représentations qui sont elles-mêmes primitives. Les textes descriptifs sont donc fictionnels par degré. Les récits qui sont très fictionnels ont une certaine valeur (souvent ludique) mais contiennent toujours au moins une facette. En fin de compte, toutes les activités représentationnelles devraient être considérées irréelles, incomplètes, bien que parfois connectées à la réalité, c’est-à-dire, prises entre une description réaliste facettée et une fiction dans son intégralité.

A Mediated Presence : Uncovering Nietzsche in Art History from its Foundations to Contemporary Anglo-American Curricula

La pensée de Nietzsche a joué un rôle déterminant et récurrent dans les discours et les débats qui ont formé et continuent de façonner le domaine de l’histoire de l’art, mais aucune analyse systématique de cette question n’a encore vu le jour. L’influence de Nietzsche a été médiée par divers interlocuteurs, historiens de l’art et philosophes, qui ont encadré ces discussions, en utilisant les écrits du philosophe comme toile de fond de leurs propres idées. Ce mémoire souhaite démontrer que l’impact de Nietzsche dans le champ de l’histoire de l’art existe mais qu’il fut toujours immergé ou éclipsé, particulièrement dans le contexte anglo-américain, l’emphase étant placée sur les médiateurs de ses idées en n’avouant que très peu d’engagement direct avec son œuvre. En conséquence, son importance généalogique pour certains fondateurs de la discipline reste méconnue; sa présence réellement féconde se traduit plutôt comme une absence ou une présence masquée. En vue de démontrer ce propos, nous regardons donc le contexte nietzschéen qui travaille les écrits de certains historiens de l’art, comme Jacob Burckhardt et Aby Warburg, ou des philosophes et d’écrivains ayant marqué la discipline de l’histoire de l’art (plus particulièrement dans le cadre de l’influence de la « French Theory » sur l’histoire de l’art anglo-américaine depuis la fin des années 1970) : Martin Heidegger, Michel Foucault, Jacques Derrida, Gilles Deleuze et Georges Bataille. Nous examinons certaines voies par lesquelles ses idées ont acquis une pertinence pour l’histoire de l’art avant de proposer les raisons potentielles de leur occlusion ultérieure. Nous étudions donc l’évolution des discours multiples de l’histoire comme domaine d’étude afin de situer la contribution du philosophe et de cerner où et comment ses réflexions ont croisé celles des historiens de l’art qui ont soit élargi ou redéfini les méthodes et les structures d’analyse de leur discipline. Ensuite nous regardons « l’art » de Nietzsche en le comparant avec « l’art de l’histoire de l’art » (Preziosi 2009) afin d’évaluer si ces deux expressions peuvent se rejoindre ou s’il y a fondamentalement une incompatibilité entre les deux, laquelle pourrait justifier ou éclairer la distance entre la pensée nietzschéenne sur l’art et la discipline de l’histoire de l’art telle qu’elle s’institutionnalise au moment où le philosophe rédige son œuvre.

THE WINCHESTER CENTRE FOR GLOBAL FUTURES IN ART DESIGN & MEDIA

The Winchester Centre for Global Futures in Art Design and Media highlights historical, contemporary and future roles for art, design and media within globalization. Its members build sustained collaborations with international partners in public service, the creative industries and civil society. Critically concerned with art and design practices of making, thinking and representation, the Winchester Centre actively engages in education and enterprise, exploring the contribution of media, materials and technologies to the improvement of human societies globally. Led by professors Jonathan Harris, Sean Cubitt, and Ryan Bishop, the Winchester Centre will make a decisive contribution to the work of the School and the University in future years. The Centre's inaugural professors would like to invite you now to suggest future research themes and activities. In the coming weeks details regarding the programme and prospective membership of the Winchester Centre will be made available.