Mast cells and oral inflammation

Mast cells are mobile granule-containing secretory cells that are distributed preferentially about the microvascular endothelium in oral mucosa and dental pulp. The enzyme profile of mast cells in oral tissues resembles that of skin, with most mast cells expressing the serine proteases tryptase and chymase. Mast cells in oral tissues contain the pro-inflammatory cytokine tumour necrosis factor-alpha in their granules, and release of this promotes leukocyte infiltration during evolving inflammation in several conditions, including lichen planus, gingivitis, pulpitis, and periapical inflammation, through induction of endothelial-leukocyte adhesion molecules. Mast cell synthesis and release of other mediators exerts potent immunoregulatory effects on other cell types, while several T-lymphocyte-derived cytokines influence mast cell migration and mediator release. Mast cell proteases may contribute to alterations in basement membranes in inflammation in the oral cavity, such as the disruptions that allow cytotoxic lymphocytes to enter the epithelium in oral lichen planus. A close relationship exists among mast cells, neural elements, and laminin, and this explains the preferential distribution of mast cells in tissues. Mast cells are responsive to neuropeptides and, through their interaction with neural elements, form a neural immune network with Langerhans cells in mucosal tissues. This facilitates mast cell degranulation in response to a range of immunological and non-immunological stimuli. Because mast cells play a pivotal role in inflammation, therapies that target mast cell functions could have value in the treatment of chronic inflammatory disorders in the oral cavity.

Habitat choice and vigilance behaviour of brush-tailed rock-wallabies (Petrogale penicillata) within their nocturnal foraging ranges

Habitat choice by brush-tailed rock-wallabies (Petrogale penicillata) in south-east Queensland was investigated by comparing the attributes of the nocturnal foraging locations that they selected with those of random locations within a radius of 50 m. Brush-tailed rock-wallabies were shown to select foraging locations on the basis of forage quality and/or their ability to see predators, rather than protection from predators amongst vegetation that could conceal them. Habitat choice may have been affected by limited food availability, as this study was conducted in the winter dry season. The attributes of foraging locations that brush- tailed rock-wallabies perceived as increasing their predation risk were assessed by recording the proportion of time that brush- tailed rock-wallabies spent vigilant while foraging. To measure vigilance, focal animals were observed with a night- vision scope for two minutes and the proportions of time spent vigilant and feeding were recorded. No measured feature of foraging locations was related to higher vigilance levels, suggesting that brush- tailed rock-wallabies did not alter their vigilance whether sheltered amongst grass tussocks or in open habitat, or whether feeding on good quality or poorer quality vegetation. Vigilance levels significantly declined as overnight temperatures decreased, which may have resulted from higher energy requirements of brush- tailed rock-wallabies during winter. The only factors that were found to significantly increase vigilance levels were high winds and moonlit nights. On bright nights, brush- tailed rock-wallabies were very unsettled and during high winds they often did not emerge to feed. More information is needed about how macropods detect predators at night before the effects of wind and light intensity upon vigilance can be fully understood.

Ultrastructure of the mature spermatozoa of caecilians (Amphibia : Gymnophiona)

The spermatozoa of Gymnophiona show the following autapomorphies: 1) penetration of the distal centriole by the axial fiber; 2) presence of an acrosomal baseplate; 3) presence of an acrosome seat (flattened apical end of nucleus); and 4) absence of juxta-axonemal fibers. The wide separation of the plasma membrane bounding the undulating membrane is here also considered to be apomorphic. Three plesiomorphic spermatozoal characters are recognized that are not seen in other Amphibia but occur in basal amniotes: 1) presence of mitochondria with a delicate array of concentric cristae (concentric cristae of salamander spermatozoa differ in lacking the delicate array); 2) presence of peripheral dense fibers associated with the triplets of the distal centriole; and 3) presence of a simple annulus (a highly modified, elongate annulus is present in salamander sperm). The presence of an endonuclear canal containing a perforatorium is a plesiomorphic feature of caecilian spermatozoa that is shared with urodeles, some basal anurans, sarcopterygian fish, and some amniotes. Spermatozoal synapornorphies are identified for 1) the Uraeotyphlidae and Ichthyophiidae, an 2) the Caeciliidae and Typhlonectidae, suggesting that the members of each pair of families are more closely related to each other than to other caecilians. Although caecilian spermatozoa exhibit the clear amphibian synapomorphy of the unilateral location of the undulating membrane and its axial fiber, they have no apomorphic characters that suggest a closer relationship to either the Urodela or Axiura. J. Morphol. 258:179-192, 2003. (C) 2003 Wiley-Liss, Inc.

Development of motor system dysfunction following whiplash injury

Dysfunction in the motor system is a feature of persistent whiplash associated disorders. Little is known about motor dysfunction in the early stages following injury and of its progress in those persons who recover and those who develop persistent symptoms. This study measured prospectively, motor system function (cervical range of movement (ROM), joint position error (JPE) and activity of the superficial neck flexors (EMG) during a test of cranio-cervical flexion) as well as a measure of fear of re-injury (TAMPA) in 66 whiplash subjects within 1 month of injury and then 2 and 3 months post injury. Subjects were classified at 3 months post injury using scores on the neck disability index: recovered (30). Motor system function was also measured in 20 control subjects. All whiplash groups demonstrated decreased ROM and increased EMG (compared to controls) at 1 month post injury. This deficit persisted in the group with moderate/severe symptoms but returned to within normal limits in those who had recovered or reported persistent mild pain at 3 months. Increased EMG persisted for 3 months in all whiplash groups. Only the moderate/severe group showed greater JPE, within 1 month of injury, which remained unchanged at 3 months. TAMPA scores of the moderate/severe group were higher than those of the other two groups. The differences in TAMPA did not impact on ROM, EMG or JPE. This study identifies, for the first time, deficits in the motor system, as early as 1 month post whiplash injury, that persisted not only in those reporting moderate/severe symptoms at 3 months but also in subjects who recovered and those with persistent mild symptoms. (C) 2002 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.

Computational differentiation of N-terminal signal peptides and transmembrane helices

Signal peptides and transmembrane helices both contain a stretch of hydrophobic amino acids. This common feature makes it difficult for signal peptide and transmembrane helix predictors to correctly assign identity to stretches of hydrophobic residues near the N-terminal methionine of a protein sequence. The inability to reliably distinguish between N-terminal transmembrane helix and signal peptide is an error with serious consequences for the prediction of protein secretory status or transmembrane topology. In this study, we report a new method for differentiating protein N-terminal signal peptides and transmembrane helices. Based on the sequence features extracted from hydrophobic regions (amino acid frequency, hydrophobicity, and the start position), we set up discriminant functions and examined them on non-redundant datasets with jackknife tests. This method can incorporate other signal peptide prediction methods and achieve higher prediction accuracy. For Gram-negative bacterial proteins, 95.7% of N-terminal signal peptides and transmembrane helices can be correctly predicted (coefficient 0.90). Given a sensitivity of 90%, transmembrane helices can be identified from signal peptides with a precision of 99% (coefficient 0.92). For eukaryotic proteins, 94.2% of N-terminal signal peptides and transmembrane helices can be correctly predicted with coefficient 0.83. Given a sensitivity of 90%, transmembrane helices can be identified from signal peptides with a precision of 87% (coefficient 0.85). The method can be used to complement current transmembrane protein prediction and signal peptide prediction methods to improve their prediction accuracies. (C) 2003 Elsevier Inc. All rights reserved.

Full-scale demonstration of biological nutrient removal in a single tank SBR process

Complete biological nutrient removal (BNR) in a single tank, sequencing batch reactor (SBR) process, is demonstrated here at full-scale on a typical domestic wastewater. The unique feature of the UniFed process is the introduction of the influent into the settled sludge blanket during the settling and decant periods of the SBR operation. This achieves suitable conditions for denitrification and anaerobic phosphate release which is critical to successful biological phosphorus removal, It also achieves a selector effect, which helps in generating a compact, well settling biomass in the reactor. The results of this demonstration show that it is possible to achieve well over 90% removal of GOD, nitrogen and phosphorus in such a process. Effluent quality achieved over a six-month operating period directly after commissioning was: 29 mg/l GOD, 0.5 mg/l NH4-N, 1.5 mg/l NOx-N and 1.5 mg/l PO4-P (50%-iles of daily samples). During an 8-day, intensive sampling period, the effluent BOD5 was

E2F modulates keratinocyte squamous differentiation. Implications for E2F inhibition in squamous cell carcinoma

E2F regulation is essential for normal cell cycle progression. Therefore, it is not surprising that squamous cell carcinoma cell lines (SCC) overexpress E2F1 and exhibit deregulated E2F activity when compared with normal keratinocytes. Indeed, deliberate E2F1 deregulation has been shown to induce hyperplasia and skin tumor formation. In this study, we report on a dual role for E2F as a mediator of keratinocyte proliferation and modulator of squamous differentiation. Overexpression of E2F isoforms in confluent primary keratinocyte cultures resulted in suppression of differentiation-associated markers. Moreover, we found that the DNA binding domain and the trans-activation domain of E2F1 are important in mediating suppression of differentiation. Use of a dominant/negative form of E2F1 ( E2F d/n) found that E2F inhibition alone is sufficient to suppress the activity of proliferation-associated markers but is not capable of inducing differentiation markers. However, if the E2F d/n is expressed in differentiated keratinocytes, differentiation marker activity is further induced, suggesting that E2F may act as a modulator of squamous differentiation. We therefore examined the effects of E2F d/n in a differentiation- insensitive SCC cell line. We found that treatment with the differentiating agent, 12-O-tetradecanoyl- phorbol-13-acetate (TPA), or expression of E2F d/n alone had no effect on differentiation markers. However, a combination of E2F d/n + TPA induced the expression of differentiation markers. Combined, these data indicate that E2F may play a key role in keratinocyte differentiation. These data also illustrate the unique potential of anti-E2F therapies in arresting proliferation and inducing differentiation of SCCs.

Recent advances on the role of CD40 and dendritic cells in immunity and tolerance

CD40 is a key signaling pathway for the function of B cells, monocytes, and dendritic cells in the immune system, and plays an important role in inflammatory pathways of nonhemopoietic cells. The NFkappaB family of transcription factors is a critical mediator in inflammation. NFkappaB is involved both in the regulation of CD40 expression and in cell signaling after CD40 ligation. This positive feedback loop linking NFkappaB and CD40 plays an important role in the control of the adaptive immune response, with fundamental implications for immunity and tolerance in vivo.

A novel target-field method for magnetic resonance shim coils: III. Shielded zonal and tesseral coils

This paper continues the development of a new approach for the design of shim and gradient coils, used in magnetic resonance imaging (MRI) applications. A cylindrical primary coil of radius a and length 2L is placed inside a co-axial shield cylinder of radius b. An active shielding strategy is used to create a desired target field at an arbitrarily specified (cylindrical) location within the primary coil, and to annul the field at a certain radius outside the shield. The form of the interior target field may be chosen arbitrarily by the designer, although zonal and tesseral harmonics are typically used in MRI applications. The method presented here designs coil windings on both the primary and shielding cylinders, to produce fields that conform to the specified interior target field and the annulled field exterior to the shield. An additional feature of the method presented here is that the target field inside the primary coil is matched at two different radii, to improve overall accuracy. The method is illustrated by designing several shielded shim coils, for creating higher order tesseral fields located asymmetrically within the coil. The simpler case of pure zonal fields is discussed separately and applied to the design of some higher order shielded coils.

Effects of speaking rate on EMA-derived lingual kinematics: a preliminary investigation

Electromagnetic articulography (EMA) was used to investigate how tongue movement characteristics (i.e., velocity, acceleration, duration, distance) change with. or indeed affect, increased rates of speech. Eight young adult males repeated /ta/ and /ka/ syllables first at a moderate rate that had been modelled at three syllables per second, and then 'as fast as possible'. Distance travelled by the tongue appeared to be the principal lingual kinematic feature manipulated by the group of speakers in producing increased syllable repetition rates, with velocity found to increase, decrease or remain unchanged. Acceleration remained unchanged, except in the case of increased velocity. One participant formed an exception in terms of manipulating distance by exhibiting marginally increased lingual velocities rather than distance changes. This preliminary study serves to direct future EMA-based studies of speech rate control as to the speech tasks that should be employed and the possible underlying anatomical and acoustic bases or constraints that could possibly influence the kinematic strategies employed to increase speech rate.

Electropalatographic assessment of tongue-to-palate contacts exhibited in dysarthria following traumatic brain injury: Spatial characteristics

Consonant imprecision has been reported to be a common feature of the dysarthric speech disturbances exhibited by individuals who have sustained a traumatic brain injury (TBI). Inaccurate tongue placements against the hard palate during consonant articulation may be one factor underlying the imprecision. To investigate this hypothesis, electropalatography (EPG) was used to assess the spatial characteristics of the tongue-to-palate contacts exhibited by three males (aged 23-29 years) with dysarthria following severe TBI. Five nonneurologically impaired adults served as control subjects. Twelve single-syllable words of CV or CVC construction (where initial C = /t, d, S, z, k, g/, V=/i, a/) were read aloud three times by each subject while wearing an EPG palate. Spatial characteristics were analyzed in terms of the location, pattern, and amount of tongue-to-palate contact at the frame of maximum contact during production of each consonant. The results revealed that for the majority of consonants, the patterns and locations of contacts exhibited by the TBI subjects were consistent with the contacts generated by the group of control subjects. One notable exception was one subject's production of the alveolar fricatives in which complete closure across the palate was demonstrated, rather than the characteristic groove configuration. Major discrepancies were also noted in relation to the amount of tongue-to-palate contact exhibited, with two TBI subjects consistently demonstrating increased contacts compared to the control subjects. The implications of these findings for the development of treatment programs for dysarthric speech disorders subsequent to TBI are highlighted.

An approach to verifying and debugging simulation models governed by ordinary differential equations: Part 1. Methodology for residual generation

For dynamic simulations to be credible, verification of the computer code must be an integral part of the modelling process. This two-part paper describes a novel approach to verification through program testing and debugging. In Part 1, a methodology is presented for detecting and isolating coding errors using back-to-back testing. Residuals are generated by comparing the output of two independent implementations, in response to identical inputs. The key feature of the methodology is that a specially modified observer is created using one of the implementations, so as to impose an error-dependent structure on these residuals. Each error can be associated with a fixed and known subspace, permitting errors to be isolated to specific equations in the code. It is shown that the geometric properties extend to multiple errors in either one of the two implementations. Copyright (C) 2003 John Wiley Sons, Ltd.

An approach to verifying and debugging simulation models governed by ordinary differential equations: Part 2. Residuals analysis and a case study

In Part 1 of this paper a methodology for back-to-back testing of simulation software was described. Residuals with error-dependent geometric properties were generated. A set of potential coding errors was enumerated, along with a corresponding set of feature matrices, which describe the geometric properties imposed on the residuals by each of the errors. In this part of the paper, an algorithm is developed to isolate the coding errors present by analysing the residuals. A set of errors is isolated when the subspace spanned by their combined feature matrices corresponds to that of the residuals. Individual feature matrices are compared to the residuals and classified as 'definite', 'possible' or 'impossible'. The status of 'possible' errors is resolved using a dynamic subset testing algorithm. To demonstrate and validate the testing methodology presented in Part 1 and the isolation algorithm presented in Part 2, a case study is presented using a model for biological wastewater treatment. Both single and simultaneous errors that are deliberately introduced into the simulation code are correctly detected and isolated. Copyright (C) 2003 John Wiley Sons, Ltd.

The pyramidal neuron in occipital, temporal and prefrontal cortex of the owl monkey (Aotus trivirgatus): regional specialization in cell structure

Recent studies have revealed marked regional variation in pyramidal cell morphology in primate cortex. In particular, pyramidal cells in human and macaque prefrontal cortex (PFC) are considerably more spinous than those in other cortical regions. PFC pyramidal cells in the New World marmoset monkey, however, are less spinous than those in man and macaques. Taken together, these data suggest that the pyramidal cell has become more branched and more spinous during the evolution of PFC in only some primate lineages. This specialization may be of fundamental importance in determining the cognitive styles of the different species. However, these data are preliminary, with only one New World and two Old World species having been studied. Moreover, the marmoset data were obtained from different cases. In the present study we investigated PFC pyramidal cells in another New World monkey, the owl monkey, to extend the basis for comparison. As in the New World marmoset monkey, prefrontal pyramidal cells in owl monkeys have relatively few spines. These species differences appear to reflect variation in the extent to which PFC circuitry has become specialized during evolution. Highly complex pyramidal cells in PFC appear not to have been a feature of a common prosimian ancestor, but have evolved with the dramatic expansion of PFC in some anthropoid lineages.

Dendritic branching of pyramidal cells in the visual cortex of the nocturnal owl monkey: A fractal analysis

The branching structure of neurones is thought to influence patterns of connectivity and how inputs are integrated within the arbor. Recent studies have revealed a remarkable degree of variation in the branching structure of pyramidal cells in the cerebral cortex of diurnal primates, suggesting regional specialization in neuronal function. Such specialization in pyramidal cell structure may be important for various aspects of visual function, such as object recognition and color processing. To better understand the functional role of regional variation in the pyramidal cell phenotype in visual processing, we determined the complexity of the dendritic branching pattern of pyramidal cells in visual cortex of the nocturnal New World owl monkey. We used the fractal dilation method to quantify the branching structure of pyramidal cells in the primary visual area (V1), the second visual area (V2) and the caudal and rostral subdivisions of inferotemporal cortex (ITc and ITr, respectively), which are often associated with color processing. We found that, as in diurnal monkeys, there was a trend for cells of increasing fractal dimension with progression through these cortical areas. The increasing complexity paralleled a trend for increasing symmetry. That we found a similar trend in both diurnal and nocturnal monkeys suggests that it was a feature of a common anthropoid ancestor.