Change blindness: eradication of gestalt strategies

Arrays of eight, texture-defined rectangles were used as stimuli in a one-shot change blindness (CB) task where there was a 50% chance that one rectangle would change orientation between two successive presentations separated by an interval. CB was eliminated by cueing the target rectangle in the first stimulus, reduced by cueing in the interval and unaffected by cueing in the second presentation. This supports the idea that a representation was formed that persisted through the interval before being 'overwritten' by the second presentation (Landman et al, 2003 Vision Research 43149–164]. Another possibility is that participants used some kind of grouping or Gestalt strategy. To test this we changed the spatial position of the rectangles in the second presentation by shifting them along imaginary spokes (by ±1 degree) emanating from the central fixation point. There was no significant difference seen in performance between this and the standard task [F(1,4)=2.565, p=0.185]. This may suggest two things: (i) Gestalt grouping is not used as a strategy in these tasks, and (ii) it gives further weight to the argument that objects may be stored and retrieved from a pre-attentional store during this task

Biology of pancreatic stellate cells—more than just pancreatic cancer

Pancreatic stellate cells, normally quiescent, are capable of remarkable transition into their activated myofibroblast-like phenotype. It is now commonly accepted that these cells play a pivotal role in the desmoplastic reaction present in severe pancreatic disorders. In recent years, enormous scientific effort has been devoted to understanding their roles in pancreatic cancer, which continues to remain one of the most deadly diseases. Therefore, it is not surprising that considerably less attention has been given to studying physiological functions of pancreatic stellate cells. Here, we review recent advances not only in the field of pancreatic stellate cell pathophysiology but also emphasise their roles in physiological processes

18th Fungal Genetics Conference

Abstracts from the 18th Fungal Genetics Conference, March 21-26, 199

Investigating Visual to Auditory Crossmodal Compensation in a Model For Acute Blindness

This study examined neural integration of the sensory modalities of vision and hearing. The objective is to investigate whether an effect of cross-modal compensation of visual to auditory networks in human participants occurs with the deprivation of visual input. This model for acute blindness had a novel design that attempted to imitate true blindness. The experiment involved 10 participants wearing opaque contact lenses that blocked visual feedback for a total of five hours. The duration of the total experiment was approximately eight hours, and involved seven sessions. The overall accuracy across time did not improve in blind individuals (p = 0.586), however, there was a significant finding in speaker accuracy (p<0.000), and a significant interaction between session and speaker (p=0.004). Reaction time generated a main effect of session (p<0.000) and a significant main effect of speaker (p<0.000), but no significant interaction between session and speaker with respect to reaction time

Cell Death, Inflammation and Oxidative Stress in Neurodegenerative Diseases

Neurogenerative diseases encompass very different pathologies, which can be demyelinating or nondemyelinating, but which have common mechanisms such as cell death, oxidative stress and inflammation. A better understanding of these mechanisms allows the search for biomarkers and targets for new therapies. This special issue brings together different data on Alzheimer's disease, Parkinson's disease, and multiple sclerosis, detailing the mechanisms of cell death (necroptosis, ferroptosis), oxidative stress and inflammation but also the possibilities of neuroprotection via 5 research articles and 6 review articles. The different reviews allow us to take stock of cell death, oxidative stress and neuroinflammation in the context of neurodegenerative diseases but also in relation to other pathologies where these processes are involved

Novel applications of shotgun phage display

In a shotgun phage display library, theoretically, the entire proteome of a bacterium is represented. Phages displaying specific polypeptides can be isolated by affinity selection, while the corresponding gene remains physically linked to the gene product. The overall objective of the study in this thesis was to explore the shotgun phage display technique in new areas. Initially, it was used to study interactions between Staphylococcus aureus and an in vivo coated biomaterial. It was shown to be well suited for the identification of bacterial proteins that bind to ex vivo central venous catheters. Several known interactions were detected, but it was also found that β2-glycoprotein I (β2-GPI) is deposited on this type of biomaterial – a finding that is of interest both for the adherence of S. aureus, but perhaps also in view of the occurrence of autoantibodies in certain autoimmune diseases. Further, it is of interest to identify the subset of extracellular proteins in a bacterium since they are involved in important functions like pathogenesis and symbiosis. A method that allows for the rapid and general isolation of extracellular proteins is desirable, and may prove particularly useful when applied to bacteria for which the genome sequences are not known. For this purpose, a specialised phage display method was developed to isolate extracellular proteins by virtue of the presence of signal peptides (SS phage display). It was successfully applied to S. aureus and, on a larger scale, to the symbiotic bacterium Bradyrhizobium japonicum. In elaboration of the SS phage display method, an inducible antisense RNA system was incorporated to enable gene silencing of the isolated genes. A tetracycline-regulated promoter was inserted in such a way, that an antisense RNA covering the cloned gene could be expressed. The new element was shown to be compatible with the properties of SS phage display, and to promote gene expression upon induction on both the transcriptional and translational level. However, screening for clones affected by the induction of antisense RNA transcription was unsuccessful, and further developments of the system are required to improve the efficiency of this attractive application

Defining the role of mast cells in guinea pig models of asthma

Asthma is a common respiratory disease characterized by several pathophysiological features, such as allergen induced bronchoconstriction (in allergic asthma), airway hyperresponsiveness (AHR), airway inflammation, airway remodeling and mast cell hyperplasia. An increase of mast cells has been found in asthma patients. However, how these cells are involved in the development of asthma are not well defined. To investigate the role of mast cells in the pathophysiological characteristics of asthma, we established asthma models in guinea pigs, which have many similarities with humans, by exposing the animals to human relevant allergens: house dust mite (HDM) and cat dander extract (CDE). The involvement of mast cells in asthma-like features was investigated either by the addition of mast cell mediator antagonists or inhibitors, or inducing mast cell death. In paper I, we repeatedly exposed guinea pigs to HDM via intranasal instillation for seven weeks and successfully recaptured the antigen induced bronchoconstriction, the production of HDM specific immunoglobulins, AHR, eosinophilic inflammation with an increase of IL-13, airway remodeling (e.g., subepithelial collagen deposition and goblet cell hyperplasia) and mast cell hyperplasia. This model can be further used to study the role of mast cells in asthma. In paper II, we exposed guinea pigs to HDM or CDE intranasally for different time. Both HDM and CDE induce airway inflammation and airway remodeling after 4 weeks’ antigen exposures. These increases maintained after 8- and 12-week exposures. Exposing to both antigens for 8 weeks and 12 weeks induced a clear expansion of mast cells which is predominated by mast cells expressing tryptase. An increase of mast cells expressing both tryptase and chymase were also observed. In paper III, we isolated guinea pig trachea for comparing the effect of different mast cell agonists (HDM and Compound 48/80 (C48/80)) on airway smooth muscle responses and mediator release. We found that histamine, prostaglandins and 5- lipoxygenase products mediated the bronchoconstriction induced by HDM and C48/80. Both agonists induced a release of histamine, prostaglandin D2 and leukotriene B4. However, distinct of lipid mediator profiles were observed. The leukotriene E4 was only elevated by HDM, whereas C48/80 induced a broader release of lipid mediators. In paper IV and V, we identified an antibiotic monensin that can induce mast cell death. To examine if monensin can be a tool for investigating the role of mast cells in asthma, we cultured guinea pig tracheal segments from HDM sensitized guinea pigs and human bronchi with different concentrations of monensin for different time. We found that monensin has robust effects on causing mast cell death and totally blocked the HDM (in guinea pig trachea) and anti-IgE (in human bronchi) induced bronchoconstriction after 2 to 72h exposure without affecting the general tissue viability at low concentration. In the in vivo investigations, we exposed the guinea pigs to HDM repeatedly with or without monensin interventions. Monensin reduced the AHR, airway inflammation and mast cell hyperplasia in the HDM induced guinea pig model. In conclusion, exposing to human relevant allergens (HDM and CDE) are suitable for modeling of allergic asthma in guinea pigs. The increase of mast cells by HDM and CDE helps to investigate the role of mast cells in asthma models. Mast cells in guinea pig airways can respond differently to antigen and non-antigen agonists. Monensin can be a robust tool to induce mast cell death. The antigen induced bronchoconstriction by HDM in guinea pig trachea and anti-IgE in human bronchi are purely mast cell mediated. Our findings emphasize that mast cells have important roles in the development of AHR and airway inflammation in the guinea pig model used in this PhD study. The findings in this thesis highlight the importance of mast cells in asthma and the models we developed can be used as important tools for defining the mechanisms behind asthma