Characterization of Endoproteolytic Processing of Dynorphins by Proprotein Convertases using Mouse Spinal Cord S9 Fractions and Mass Spectrometry

Dynorphins are important neuropeptides with a central role in nociception and pain alleviation. Many mechanisms regulate endogenous dynorphin concentrations, including proteolysis. Proprotein convertases (PCs) are widely expressed in the central nervous system and specifically cleave at C-terminal of either a pair of basic amino acids, or a single basic residue. The proteolysis control of endogenous Big Dynorphin (BDyn) and Dynorphin A (Dyn A) levels has a profound impact on pain perception and the role of PCs remain unclear. The objective of this study was to decipher the role of PC1 and PC2 in the proteolysis control of BDyn and Dyn A levels using cellular fractions of spinal cords from wild type (WT), PC1-/+ and PC2-/+ animals and mass spectrometry. Our results clearly demonstrate that both PC1 and PC2 are involved in the proteolysis regulation of BDyn and Dyn A with a more important role for PC1. C-terminal processing of BDyn generates specific peptide fragments Dynorphin 1-19, Dynorphin 1-13, Dynorphin 1-11 and Dynorphin 1-7 and C-terminal processing of Dyn A generates Dynorphin 1-13, Dynorphin 1-11 and Dynorphin 1-7, all these peptide fragments are associated with PC1 or PC2 processing. Moreover, proteolysis of BDyn leads to the formation of Dyn A and Leu-Enk, two important opioid peptides. The rate of formation of both is significantly reduced in cellular fractions of spinal cord mutant mice. As a consequence, even partial inhibition of PC1 or PC2 may impair the endogenous opioid system.

Application of central composite rotatable design to modelling the effect of some operating variables on the performance of the three-product cyclone

The central composite rotatable design (CCRD) was used to design an experimental program to model the effects of inlet pressure, feed density, and length and diameter of the inner vortex finder on the operational performance of a 150-min three-product cyclone. The ranges of values of the variables used in the design were: inlet pressure: 80-130 kPa, feed density: 30 60%; length of IVF below the OVF: 50-585 mm; diameter of IVF: 35-50 mm. A total of 30 tests were conducted, which is 51 less; an that required for a three-level full factorial design. Because the model allows confident performance prediction by interpolation over the range of data in the database, it was used to construct response surface graphs to describe the effects of the variables on the performance of the three-product cyclone. To obtain a simple and yet a realistic model, it was refitted using only the variable terms that are significant at greater than or equal to 90% confidence level. Considering the selected operating variables, the resultant model is significant and predicts the experimental data well. (c) 2005 Elsevier B.V. All rights reserved.

Morningness-eveningness orientation, optimal time-of-day and attitude change: Evidence for the systematic processing of a persuasive communication

This study investigates the effects of morningness-eveningness orientation and time-of-day on persuasion. In an attitude change paradigm, 120 female participants read a persuasive message that consisted of six counter-attitudinal arguments (anti-voluntary euthanasia) either in the morning (8:30 a.m.) or in the evening (7:00 p.m.). Attitude change was assessed by measuring attitudes towards the target issue before and after exposure to the message. Message processing was assessed by thought-listing and message recall tasks. Self-reported mood and arousal were monitored throughout. Participants were classified into M- and E-types according to their scores on the Horne and Ostberg (1976) MEQ questionnaire. When tested at their respective optimal time-of-day (i.e., morning for M-types/evening for E-types), M- and E-types reported higher energetic arousal, greater agreement with the message, greater message-congruent thinking, and a propensity for superior message recall compared to M- and E-types tested at their nonoptimal time-of-day (i.e., evening for M-types/morning for E-types). The attitude change in those tested at their optimal time-of-day was mediated by the level of message-congruent thinking. Results are interpreted in terms of the Elaboration Likelihood Model of persuasion. (c) 2005 Elsevier Ltd. All rights reserved.

Central hypersensitivity in whiplash: Implications for physiotherapy assessment and management

It is emerging that whiplash-associated disorder (WAD) is a complex condition characterised by a variety of physical and psychological features. Generalised sensory hypersensitivity is one of these features and its presence reflects augmented central pain processing mechanisms. Whilst most studies have investigated these processes in chronic WAD, it is becoming clear that in some of the whiplash injured, sensory disturbances are present from soon after injury, and are associated with both poor recovery and recalcitrance to multimodal physiotherapy interventions. Evidence for sensory hypersensitivity in WAD and possible underlying mechanisms of these phenomena are reviewed. Physiotherapists play an important role in the evaluation and management of whiplash injury. It is important that sensory disturbances be identified early in the clinical assessment of the whiplash injured patient and that ensuing management strategies address these changes, if the aim of treatment is to prevent the transition to chronicity.

Specializations of the granular prefrontal cortex of primates: Implications for cognitive processing

The biological underpinnings of human intelligence remain enigmatic. There remains the greatest confusion and controversy regarding mechanisms that enable humans to conceptualize, plan, and prioritize, and why they are set apart from other animals in their cognitive abilities. Here we demonstrate that the basic neuronal building block of the cerebral cortex, the pyramidal cell, is characterized by marked differences in structure among primate species. Moreover, comparison of the complexity of neuron structure with the size of the cortical area/region in which the cells are located revealed that trends in the granular prefrontal cortex (gPFC) were dramatically different to those in visual cortex. More specifically, pyramidal cells in the gPFC of humans had a disproportionately high number of spines. As neuron structure determines both its biophysical properties and connectivity, differences in the complexity in dendritic structure observed here endow neurons with different computational abilities. Furthermore, cortical circuits composed of neurons with distinguishable morphologies will likely be characterized by different functional capabilities. We propose that 1. circuitry in V1, V2, and gPFC within any given species differs in its functional capabilities and 2. there are dramatic differences in the functional capabilities of gPFC circuitry in different species, which are central to the different cognitive styles of primates. In particular, the highly branched, spinous neurons in the human gPFC may be a key component of human intelligence. (C) 2005 Wiley-Liss, Inc.

Sensory Processing in Aquatic Environments

Research on sensory processing or the way animals see, hear, smell, taste, feel and electrically and magnetically sense their environment has advanced a great deal over the last fifteen years. This book discusses the most important themes that have emerged from recent research and provides a summary of likely future directions. The book starts with two sections on the detection of sensory signals over long and short ranges by aquatic animals, covering the topics of navigation, communication, and finding food and other localized sources. The next section, the co-evolution of signal and sense, deals with how animals decide whether the source is prey, predator or mate by utilizing receptors that have evolved to take full advantage of the acoustical properties of the signal. Organisms living in the deep-sea environment have also received a lot of recent attention, so the next section deals with visual adaptations to limited light environments where sunlight is replaced by bioluminescence and the visual system has undergone changes to optimize light capture and sensitivity. The last section on central co-ordination of sensory systems covers how signals are processed and filtered for use by the animal. This book will be essential reading for all researchers and graduate students interested in sensory systems.

Thalamic paraventricular nucleus lesions facilitate central amygdala neuronal responses to acute psychological stress

The thalamic paraventricular nucleus (PVT) is activated by stress and projects to forebrain structures directly implicated in processing stress-related information. Accordingly, it seems likely the PVT plays an important role in modulating stress responses. We examined effects of excitotoxic PVT lesions on forebrain Fos expression patterns normally elicited by an acute psychological stressor. PVT lesions significantly increased stress-induced Fos in a key stress-processing region, the central amygdala.

Monitoring Infants By Automatic Video Processing

This work has, as its objective, the development of non-invasive and low-cost systems for monitoring and automatic diagnosing specific neonatal diseases by means of the analysis of suitable video signals. We focus on monitoring infants potentially at risk of diseases characterized by the presence or absence of rhythmic movements of one or more body parts. Seizures and respiratory diseases are specifically considered, but the approach is general. Seizures are defined as sudden neurological and behavioural alterations. They are age-dependent phenomena and the most common sign of central nervous system dysfunction. Neonatal seizures have onset within the 28th day of life in newborns at term and within the 44th week of conceptional age in preterm infants. Their main causes are hypoxic-ischaemic encephalopathy, intracranial haemorrhage, and sepsis. Studies indicate an incidence rate of neonatal seizures of 0.2% live births, 1.1% for preterm neonates, and 1.3% for infants weighing less than 2500 g at birth. Neonatal seizures can be classified into four main categories: clonic, tonic, myoclonic, and subtle. Seizures in newborns have to be promptly and accurately recognized in order to establish timely treatments that could avoid an increase of the underlying brain damage. Respiratory diseases related to the occurrence of apnoea episodes may be caused by cerebrovascular events. Among the wide range of causes of apnoea, besides seizures, a relevant one is Congenital Central Hypoventilation Syndrome (CCHS) \cite{Healy}. With a reported prevalence of 1 in 200,000 live births, CCHS, formerly known as Ondine's curse, is a rare life-threatening disorder characterized by a failure of the automatic control of breathing, caused by mutations in a gene classified as PHOX2B. CCHS manifests itself, in the neonatal period, with episodes of cyanosis or apnoea, especially during quiet sleep. The reported mortality rates range from 8% to 38% of newborn with genetically confirmed CCHS. Nowadays, CCHS is considered a disorder of autonomic regulation, with related risk of sudden infant death syndrome (SIDS). Currently, the standard method of diagnosis, for both diseases, is based on polysomnography, a set of sensors such as ElectroEncephaloGram (EEG) sensors, ElectroMyoGraphy (EMG) sensors, ElectroCardioGraphy (ECG) sensors, elastic belt sensors, pulse-oximeter and nasal flow-meters. This monitoring system is very expensive, time-consuming, moderately invasive and requires particularly skilled medical personnel, not always available in a Neonatal Intensive Care Unit (NICU). Therefore, automatic, real-time and non-invasive monitoring equipments able to reliably recognize these diseases would be of significant value in the NICU. A very appealing monitoring tool to automatically detect neonatal seizures or breathing disorders may be based on acquiring, through a network of sensors, e.g., a set of video cameras, the movements of the newborn's body (e.g., limbs, chest) and properly processing the relevant signals. An automatic multi-sensor system could be used to permanently monitor every patient in the NICU or specific patients at home. Furthermore, a wire-free technique may be more user-friendly and highly desirable when used with infants, in particular with newborns. This work has focused on a reliable method to estimate the periodicity in pathological movements based on the use of the Maximum Likelihood (ML) criterion. In particular, average differential luminance signals from multiple Red, Green and Blue (RGB) cameras or depth-sensor devices are extracted and the presence or absence of a significant periodicity is analysed in order to detect possible pathological conditions. The efficacy of this monitoring system has been measured on the basis of video recordings provided by the Department of Neurosciences of the University of Parma. Concerning clonic seizures, a kinematic analysis was performed to establish a relationship between neonatal seizures and human inborn pattern of quadrupedal locomotion. Moreover, we have decided to realize simulators able to replicate the symptomatic movements characteristic of the diseases under consideration. The reasons is, essentially, the opportunity to have, at any time, a 'subject' on which to test the continuously evolving detection algorithms. Finally, we have developed a smartphone App, called 'Smartphone based contactless epilepsy detector' (SmartCED), able to detect neonatal clonic seizures and warn the user about the occurrence in real-time.

Is the generation of neo-antigenic determinants by free radicals central to the development of autoimmune rheumatoid disease?

Biomolecules are susceptible to many different post-translational modifications that have important effects on their function and stability, including glycosylation, glycation, phosphorylation and oxidation chemistries. Specific conversion of aspartic acid to its isoaspartyl derivative or arginine to citrulline leads to autoantibody production in models of rheumatoid disease, and ensuing autoantibodies cross-react with native antigens. Autoimmune conditions associate with increased activation of immune effector cells and production of free radical species via NADPH oxidases and nitric oxide synthases. Generation of neo-antigenic determinants by reactive oxygen and nitrogen species ROS and RNS) may contribute to epitope spreading in autoimmunity. The oxidation of amino acids by peroxynitrite, hypochlorous acid and other reactive oxygen species (ROS) increases the antigenicity of DNA, LDL and IgG, generating ligands for which autoantibodies show higher avidity. This review focuses on the evidence for ROS and RNS in promoting the autoimmune responses observed in diseases rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). It considers the evidence for ROS/RNS-induced antigenicity arising as a consequence of failure to remove or repair ROS/RNS damaged biomolecules and suggests that an associated defect, probably in T cell signal processing or/or antigen presentation, is required for the development of disease.

Contextual effects in speed perception may occur at an early stage of processing

How does nearby motion affect the perceived speed of a target region? When a central drifting Gabor patch is surrounded by translating noise, its speed can be misperceived over a fourfold range. Typically, when a surround moves in the same direction, perceived centre speed is reduced; for opposite-direction surrounds it increases. Measuring this illusion for a variety of surround properties reveals that the motion context effects are a saturating function of surround speed (Experiment I) and contrast (Experiment II). Our analyses indicate that the effects are consistent with a subtractive process, rather than with speed being averaged over area. In Experiment III we exploit known properties of the motion system to ask where these surround effects impact. Using 2D plaid stimuli, we find that surround-induced shifts in perceived speed of one plaid component produce substantial shifts in perceived plaid direction. This indicates that surrounds exert their influence early in processing, before pattern motion direction is computed. These findings relate to ongoing investigations of surround suppression for direction discrimination, and are consistent with single-cell findings of direction-tuned suppressive and facilitatory interactions in primary visual cortex (V1).

Morphology in autism spectrum disorders:local processing bias and language

We conducted a detailed study of a case of linguistic talent in the context of autism spectrum disorder, specifically Asperger syndrome. I.A. displays language strengths at the level of morphology and syntax. Yet, despite this grammar advantage, processing of figurative language and inferencing based on context presents a problem for him. The morphology advantage for I.A. is consistent with the weak central coherence (WCC) account of autism. From this account, the presence of a local processing bias is evident in the ways in which autistic individuals solve common problems, such as assessing similarities between objects and finding common patterns, and may therefore provide an advantage in some cognitive tasks compared to typical individuals. We extend the WCC account to language and provide evidence for a connection between the local processing bias and the acquisition of morphology and grammar.

Face context interferes with local part processing in a prosopagnosic patient

We investigated the role of local and global information on perceptual encoding of faces in patient HJA, who shows prosopagnosia and visual agnosia following occipito-temporal damage. HJA and an age-matched control were tested in a simultaneous matching task which focused on detection of local changes in faces: the inversion of central parts (eyes and mouth) relative to their context (as in the Thatcher illusion). Same-different judgements were made to normal, “thatcherised” and mixed type face pairs. Whole faces (Experiment 1), or face parts (Experiment 2), were presented in upright and inverted orientations. Compared to the control, HJA was severely impaired at matching whole faces, but he improved dramatically when face parts were presented in isolation. This suggests an inhibitory influence of face context on HJAs processing of local parts and a relatively intact ability to process part-based information from a face (when context cannot interfere). Face inversion did not affect HJAs performance. A control experiment (Experiment 3) with non-face stimuli (houses) suggested that the inhibitory influence of context on HJAs performance was restricted to faces. These results indicate that contextual information in a face can have an adverse influence on the processing of local part-based information in prosopagnosia.

Changes in information processing in children and their implications for marketing strategy

This thesis examines children's consumer choice behaviour using an information processing perspective, with the fundamental goal of applying academic research to practical marketing and commercial problems. Proceeding a preface, which describes the academic and commercial terms of reference within which this interdisciplinary study is couched, the thesis comprises four discernible parts. Initially, the rationale inherent in adopting an information processing perspective is justified and the diverse array of topics which have bearing on children's consumer processing and behaviour are aggregated. The second part uses this perspective as a springboard to appraise the little explored role of memory, and especially memory structure, as a central cognitive component in children's consumer choice processing. The main research theme explores the ease with which 10 and 11 year olds retrieve contemporary consumer information from subjectively defined memory organisations. Adopting a sort-recall paradigm, hierarchical retrieval processing is stimulated and it is contended that when two items, known to be stored proximally in the memory organisation are not recalled adjacently, this discrepancy is indicative of retrieval processing ease. Results illustrate the marked influence of task conditions and orientation of memory structure on retrieval; these conclusions are accounted for in terms of input and integration failure. The third section develops the foregoing interpellations in the marketing context. A straightforward methodology for structuring marketing situations is postulated, a basis for segmenting children's markets using processing characteristics is adopted, and criteria for communicating brand support information to children are discussed. A taxonomy of market-induced processing conditions is developed. Finally, a case study with topical commercial significance is described. The development, launch and marketing of a new product in the confectionery market is outlined, the aetiology of its subsequent demise identified and expounded, and prescriptive guidelines are put forward to help avert future repetition of marketing misjudgements.

UncertWeb processing service:making models easer to access on the web

Models are central tools for modern scientists and decision makers, and there are many existing frameworks to support their creation, execution and composition. Many frameworks are based on proprietary interfaces, and do not lend themselves to the integration of models from diverse disciplines. Web based systems, or systems based on web services, such as Taverna and Kepler, allow composition of models based on standard web service technologies. At the same time the Open Geospatial Consortium has been developing their own service stack, which includes the Web Processing Service, designed to facilitate the executing of geospatial processing - including complex environmental models. The current Open Geospatial Consortium service stack employs Extensible Markup Language as a default data exchange standard, and widely-used encodings such as JavaScript Object Notation can often only be used when incorporated with Extensible Markup Language. Similarly, no successful engagement of the Web Processing Service standard with the well-supported technologies of Simple Object Access Protocol and Web Services Description Language has been seen. In this paper we propose a pure Simple Object Access Protocol/Web Services Description Language processing service which addresses some of the issues with the Web Processing Service specication and brings us closer to achieving a degree of interoperability between geospatial models, and thus realising the vision of a useful 'model web'.