The Function and Structure of the Marsupial Enamel

The aims of this study are to clarify the structure of tubular enamel and the function of enamel tubules on the marsupial of opossum (Monodelphis domestica). Almost all enamel prisms, surrounded by interprismatic enamel, ran obliquely from the dentinoenamel junction (DEJ), and bent near the enamel surface. The enamel tubules are distributed in both enamel prisms and the interprismatic enamel near the DEJ. From the middle to the surface of the enamel, one enamel tubule ran within a single enamel prism. Most of enamel tubules continued from the DEJ to near the enamel surface. It is suggested that each enamel tubule developed in relation to one ameloblast. The fibers of odontoblastic process penetrated the DEJ from the dentinal tubules into the enamel tubules, and some branched across the enamel prisms. The odontoblastic process may be actively cross into the ameloblastic layer and may be involved in the formation of enamel tubules. After in vivo injection of tetracycline, tetracycline labeling showed that the odontoblastic tubules continued to enamel tubules. And strontium was detected in enamel tubules from the DEJ to the enamel surface, as was the dentinal tubules. In conclusion, there was active transport by the odontoblast and it's process through the enamel tubules.     

The function and structure of the marsupial enamel

The aims of this study are to clarify the structure of tubular enamel and the function of enamel tubules on the marsupial of opossum (Monodelphis domestica). Almost all enamel prisms, surrounded by interprismatic enamel, ran obliquely from the dentinoenamel junction (DEJ), and bent near the enamel surface. The enamel tubules are distributed in both enamel prisms and the interprismatic enamel near the DEJ. From the middle to the surface of the enamel, one enamel tubule ran within a single enamel prism. Most of enamel tubules continued from the DEJ to near the enamel surface. It is suggested that each enamel tubule developed in relation to one ameloblast. The fibers of odontoblastic process penetrated the DEJ from the dentinal tubules into the enamel tubules, and some branched across the enamel prisms. The odontoblastic process may be actively cross into the ameloblastic layer and may be involved in the formation of enamel tubules. After in vivo injection of tetracycline, tetracycline labeling showed that the odontoblastic tubules continued to enamel tubules. And strontium was detected in enamel tubules from the DEJ to the enamel surface, as was the dentinal tubules. In conclusion, there was active transport by the odontoblast and it's process through the enamel tubules.     

Quantal encoding of information in a retinal ganglion cell

A retinal ganglion cell receives information about a white-noise stimulus as a flickering pattern of glutamate quanta. The ganglion cell reencodes this information as brief bursts of one to six spikes separated by quiescent periods. When the stimulus is repeated, the number of spikes in a burst is highly reproducible (variance < mean) and spike timing is precise to within 10 ms, leading to an estimate that each spike encodes about 2 bits. To understand how the ganglion cell reencodes information, we studied the quantal patterns by repeating a white-noise stimulus and recording excitatory currents from a voltage-clamped, brisk-sustained ganglion cell. Quanta occurred in synchronous bursts of 3 to 65; the resulting postsynaptic currents summed to form excitatory postsynaptic currents (EPSCs). The number of quanta in an EPSC was only moderately reproducible (variance = mean), quantal timing was precise to within 14 ms, and each quantum encoded 0.1-0.4 bit. In conclusion, compared to a spike, a quantum has similar temporal precision, but is less reproducible and encodes less information. Summing multiple quanta into discrete EPSCs improves the reproducibility of the overall quantal pattern and contributes to the reproducibility of the spike train.     

Odontogenic differentiation of human dental pulp stem cells induced by preameloblast-derived factors

The differentiation of odontoblasts is initiated by the organization of differentiating ameloblasts during tooth formation. However, the exact roles of ameloblast-derived factors in odontoblast differentiation have not yet been characterized. We investigated the effects of preameloblast-conditioned medium (PA-CM) on the odontogenic differentiation of human dental pulp stem cells (hDPSCs) in?vitro and in?vivo. Furthermore, we analyzed the PA-CM by liquid chromatography-mass spectrometry to identify novel factors that facilitate odontoblast differentiation. In the co-culture of MDPC-23 cells or hDPSCs with mouse apical bud cells (ABCs), ABCs promoted differentiation of odontoblastic MDPC-23 cells and facilitated odontoblast differentiation of hDPSCs. PA-CM, CM from ABCs after 3 days culture, was most effective in increasing the dentin sialophosphoprotein promoter activity of odontoblastic MDPC-23 cells. When PA-CM-treated hDPSCs were transplanted into immunocompromised mice, they generated pulp-like structures lined with human odontoblast-like cells showing typical odontoblast processes. However, during recombinant human bone morphogenenetic protein 2-treated hDPSCs transplantation, some of the cells were entrapped in mineralized matrix possessing osteocyte characteristics. After proteomic analyses, we identified 113 types of proteins in PA-CM, of which we characterized 23. The results show that preameloblast-derived factors induce the odontogenic differentiation of hDPSCs and promote dentin formation.     

Proteomics and genetics of dental enamel

The initiation of enamel crystals at the dentino-enamel junction is associated with the expression of dentin sialophosphoprotein (DSPP, a gene normally linked with dentin formation), three 'structural' enamel proteins--amelogenin (AMELX), enamelin (ENAM), and ameloblastin (AMBN)--and a matrix metalloproteinase, enamelysin (MMP20). Enamel formation proceeds with the steady elongation of the enamel crystals at a mineralization front just beneath the ameloblast distal membrane, where these proteins are secreted. As the crystal ribbons lengthen, enamelysin processes the secreted proteins. Some of the cleavage products accumulate in the matrix, others are reabsorbed back into the ameloblast. Once crystal elongation is complete and the enamel layer reaches its final thickness, kallikrein 4 (KLK4) facilitates the breakdown and reabsorption of accumulated enamel matrix proteins. The importance of the extracellular matrix proteins to proper tooth development is best illustrated by the dramatic dental phenotypes observed in the targeted knockouts of enamel matrix genes in mice (Dspp, Amelx, Ambn, Mmp20) and in human kindreds with defined mutations in the genes (DSPP, AMELX, ENAM, MMP20, KLK4) encoding these matrix proteins. However, ablation studies alone cannot give specific mechanistic information on how enamel matrix proteins combine to catalyze the formation of enamel crystals. The best approach for determining the molecular mechanism of dental enamel formation is to reconstitute the matrix and synthesize enamel crystals in vitro. Here, we report refinements to the procedures used to isolate porcine enamel and dentin proteins, recent advances in the characterization of enamel matrix protein posttranslational modifications, and summarize the results of human genetic studies that associate specific mutations in the genes encoding matrix proteins with a range of dental phenotypes.     

Comparison of algorithms for the simulation of action potentials with stochastic sodium channels

This paper presents a comparison of computational algorithms to simulate action potentials using stochastic sodium channels. Four algorithms are compared in single-node models: Strassberg and DeFelice (1993) (SD), Rubinstein (1995) (R), Chow and White (1996) (CW), and Fox (1997) (F). Neural responses are simulated to a simple and a preconditioned monophasic current pulse. Three exact algorithms implementing Markov jumping processes (SD, R, CW) resulted in similar responses, while the approximation algorithm using Langevins equation (F) showed quite different responses from those in the exact algorithms. The computational time was measured as well: 1(F), 7(CW), 32(SD), 39(R) relative to that of the F algorithm. Furthermore, it is shown that as the sampling step for integration of the transmembrane potential increases, neural responses in all algorithms tended to be different from those in dense sampling steps, however, the CW algorithm was robust even at a sparse sampling step. It is concluded that the most computationally efficient algorithm having appropriate properties of neural excitability is the CW algorithm. © 2002 Biomedical Engineering Society. PAC2002: 8716Uv, 8716Ac, 0250Ga, 0250Ey, 0260Jh     

Quantitative magnetisation transfer imaging in glioma: preliminary results

Quantitative magnetisation transfer imaging (qMTI) is an extension of conventional MT techniques and allows the measurement of parameters that reflect tissue ultrastructure through the properties of macromolecule‐bound protons; these include the bound proton fraction and the relaxation times of free and bound proton pools. It has been used in multiple sclerosis and Alzheimer's disease, and has shown changes in some of the parameters, particularly the bound proton fraction. The purpose of this pilot study was to assess whether qMTI could distinguish between gliomas and normal brain tissue, and provide proof of principle for its use in tumour characterisation. Eight subjects [three men, five women; mean age, 44 years; range, 27–66 years; seven World Health Organization (WHO) Grade II, one Grade III] with biopsy‐proven glioma were imaged with a structural MRI protocol that included three‐dimensional qMTI. qMTI parameters were extracted from regions of interest selected from different tumour components visible on conventional MR sequences, normal‐appearing peritumoral tissue and distant normal‐appearing white matter. All patients gave informed consent and the study was approved by the Local Research Ethics Committee. Almost all of the qMTI parameters detected abnormalities in both glioma and the peritumoral region relative to the distant white matter. In particular, the bound proton fraction was reduced significantly from 6.0 percentage units (pu) [standard deviation (SD), 0.5 pu] in normal‐appearing white matter to 1.7 pu (SD = 0.5 pu) in solid tumour and 2.2 pu (SD = 0.5 pu) in peritumoral areas. This work shows that qMTI reveals abnormalities, not only in glioma, but also in the apparently normal tissue surrounding the conventionally defined tumour. Thus, qMTI shows promise for tumour characterisation and for studying tumour boundaries. These preliminary data justify larger studies in a range of different tumour types and grades. Copyright © 2010 John Wiley & Sons, Ltd.     

Mechanisms underlying interlimb transfer of visuomotor rotations

We previously reported that opposite arm training improved the initial direction of dominant arm movements, whereas it only improved the final position accuracy of non-dominant arm movements. We now ask whether each controller accesses common, or separate, short-term memory resources. To address this question, we investigated interlimb transfer of learning for visuomotor rotations that were directed oppositely [clockwise (CW)/counterclockwise (CCW)] for the two arms. We expected that if information obtained by initial training was stored in the same short-term memory space for both arms, opposite arm training of a CW rotation would interfere with subsequent adaptation to a CCW rotation. All subjects first adapted to a 30° rotation (CW) in the visual display during reaching movements. Following this, they adapted to a 30° rotation in the opposite direction (CCW) with the other arm. In contrast to our previous findings for interlimb transfer of same direction rotations (CCW/CCW), no effects of opposite arm adaptation were indicated in the initial trials performed. This indicates that interlimb transfer is not obligatory, and suggests that short-term memory resources for the two limbs are independent. Through single trial analysis, we found that the direction and final position errors of the first trial of movement, following opposite arm training, were always the same as those of naive performance. This was true whether the opposite arm was trained with the same or the opposing rotation. When trained with the same rotation, transfer of learning did not occur until the second trial. These findings suggest that the selective use of opposite arm information is dependent on the first trial to probe current movement conditions. Interestingly, the final extent of adaptation appeared to be reduced by opposite arm training of opposing rotations. Thus, the extent of adaptation, but not initial information transfer, appears obligatorily affected by prior opposite arm adaptation. According to our findings, it is plausible that the initiation and the final extent of adaptation involve two independent neural processes. Theoretical implications of these findings are discussed. Electronic Publication     

Protein Fraction with Immunogenic Potential and Low Toxicity Isolated from the Cell Wall of Neisseria meningitidis Group B

Several fractions were extracted from the cell envelope (CE) of Neisseria meningitidis group B and characterized with regard to their morphology, antigenicity, protein composition, and toxicity. Whole bacterial cells were suspended in a medium of low ionic strength and disrupted in a French pressure cell. The crude CE thus obtained were separated into cell membrane (CM) enriched and cell wall (CW) enriched fractions on sucrose density gradients. In addition, CM and CW fractions were separated from CE on the basis of differential solubility in the nonionic detergent, Triton X-100. The Triton-insoluble fraction, containing primarily CW components, was further treated with a mixture of Triton and ethylenediaminetetraacetic acid, which was shown to remove additional protein and most of the lipopolysaccharide. Electron microscope examination of the various fractions revealed typical unit membrane structures in the case of CM, or large, open segments in the case of CW. The Triton-insoluble and especially the Triton-ethylenediaminetetraacetic acid-insoluble fractions consisted of small vesicular structures. All fractions, except the Triton-soluble fraction, when assayed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, were shown to contain one major protein component accounting for more than 50% of the total. Sera from rabbits immunized with the various fractions formed precipitin lines in immunodiffusion tests against the homologous and some of the heterologous fractions. High-titer bactericidal antibodies were also demonstrated in these sera when tested against the homologous strains. Toxicity studies in rats sensitized with lead acetate indicate that the level of contamination of Triton-insoluble/Triton-ethylenediaminetetraacetic acid-insoluble fractions with lipopolysaccharide was significantly smaller than that of the other fractions.     

Delayed hypersensitivity to Staphylococcus aureus in mice: in vitro responses to isolated Staphylococcal antigens

Isolated Staphylococcal cellular components were used to evaluate the in vitro reactivity of lymphocytes from mice with delayed hypersensitivity to Staphylococcus aureus. Macrophage migration inhibition studies showed that splenic lymphocytes from mice sensitized with three injections of S. aureus inhibited macrophage migration when stimulated with S. aureus sonicate antigen (SASA), cell membrane (CM), and purified membrane protein (PMP). Continued injections (seven) resulted in migration inhibition when the sensitized cells were reacted with SASA, CM, PMP, cell wall (CW), and protein A (PA). Lymphocyte stimulation studies following three injections further illustrated the role of membrane proteins in the early phase of mouse reactivity. Splenic lymphocytes were maximally stimulated by SASA, CM, and PMP. Lipoteichoic acid (LTA), teichoic acid (TA), and CW also were stimulatory but to a much lesser degree. Mice receiving seven S. aureus injections had a high basal stimulatory response which overshadowed the responses to the isolated staphylococcal components. All of the staphylococcal components except LTA were mitogenic for splenic B lymphocytes. The mitogenicity was dependent upon the presence of macrophages. Only SASA, CM, and PMP were mitogenic for non-enriched splenic lymphocytes.     

Expression,structure, and function of enamel proteinases

Proteinases serve two important functions during dental enamel formation: They (a) process and (b) degrade enamel proteins. Different enzymes carry out these functions. Enamelysin (MMP-20) is the foremost enamel matrix-processing enzyme. Its expression initiates prior to the onset of dentin mineralization and continues throughout the secretory stage of amelogenesis. In vitro, enamelysin catalyzes all of the amelogenin cleavages that are known to occur during the secretory stage in vivo, and it is probably the enzyme responsible for the processing of all enamel proteins. There is evidence suggesting that enamelysin activity is critical for proper enamel formation. Uncleaved and processed enamel proteins often segregate into different compartments within the developing enamel layer, suggesting that they may have different functions. Intact ameloblastin and its C-terminal cleavage products localize in the superficial rod and interrod enamel, while its N-terminal cleavage products congregate in the sheath space. Intact enamelin is only present at the mineralization front within a micrometer of the enamel surface, while its cleavage products concentrate in the rod and interrod enamel. Processed enamel proteins accumulate during the secretory stage, but disappear early in the maturation stage. Enamel matrix serine proteinase 1 (EMSP1), now officially designated kallikrein 4 (KLK4), is believed to be the predominant degradative enzyme that clears enamel proteins from the matrix during maturation. KLK4 expression initiates during the transition stage and continues throughout maturation. KLK4 concentrates at the enamel surface when the enamel matrix disappears, and aggressively degrades amelogenin in vitro. During tooth development, proteinases are secreted by ameloblasts into the extracellular space, where they cleave enamel proteins by catalyzing the hydrolysis of peptide bonds. Enamel proteinases are present in low abundance and are not likely to participate directly in the mineralization process. Two major enamel proteinases have been identified: enamelysin (MMP20) and kallikrein 4 (KLK4). These proteinases are expressed at different times and have different functions. Their roles are to modify and/or to eliminate enamel matrix proteins, which affects the way enamel proteins interact with each other and with the developing enamel crystallites. A brief review of dental enamel formation is presented, followed by a more detailed analysis of enamelysin and KLK4 expression, structure, and function.     

Expression,Structure, and Function of Enamel Proteinases

Proteinases serve two important functions during dental enamel formation: They (a) process and (b) degrade enamel proteins. Different enzymes carry out these functions. Enamelysin (MMP-20) is the foremost enamel matrix-processing enzyme. Its expression initiates prior to the onset of dentin mineralization and continues throughout the secretory stage of amelogenesis. In vitro, enamelysin catalyzes all of the amelogenin cleavages that are known to occur during the secretory stage in vivo, and it is probably the enzyme responsible for the processing of all enamel proteins. There is evidence suggesting that enamelysin activity is critical for proper enamel formation. Uncleaved and processed enamel proteins often segregate into different compartments within the developing enamel layer, suggesting that they may have different functions. Intact ameloblastin and its C-terminal cleavage products localize in the superficial rod and interrod enamel, while its N-terminal cleavage products congregate in the sheath space. Intact enamelin is only present at the mineralization front within a micrometer of the enamel surface, while its cleavage products concentrate in the rod and interrod enamel. Processed enamel proteins accumulate during the secretory stage, but disappear early in the maturation stage. Enamel matrix serine proteinase 1 (EMSP1), now officially designated kallikrein 4 (KLK4), is believed to be the predominant degradative enzyme that clears enamel proteins from the matrix during maturation. KLK4 expression initiates during the transition stage and continues throughout maturation. KLK4 concentrates at the enamel surface when the enamel matrix disappears, and aggressively degrades amelogenin in vitro. During tooth development, proteinases are secreted by ameloblasts into the extracellular space, where they cleave enamel proteins by catalyzing the hydrolysis of peptide bonds. Enamel proteinases are present in low abundance and are not likely to participate directly in the mineralization process. Two major enamel proteinases have been identified: enamelysin (MMP20) and kallikrein 4 (KLK4). These proteinases are expressed at different times and have different functions. Their roles are to modify and/or to eliminate enamel matrix proteins, which affects the way enamel proteins interact with each other and with the developing enamel crystallites. A brief review of dental enamel formation is presented, followed by a more detailed analysis of enamelysin and KLK4 expression, structure, and function.     

Alteration of dentin–enamel mechanical properties due to dental whitening treatments

The mechanical properties of dentin and enamel affect the reliability and wear properties of a tooth. This study investigated the influence of clinical dental treatments and procedures, such as whitening treatments or etching prior to restorative procedures. Both autoclaved and non-autoclaved teeth were studied in order to allow for both comparison with published values and improved clinical relevance. Nanoindentation analysis with the Oliver–Pharr model provided elastic modulus and hardness across the dentin–enamel junction (DEJ). Large increases were observed in the elastic modulus of enamel in teeth that had been autoclaved (52.0 GPa versus 113.4 GPa), while smaller increases were observed in the dentin (17.9 GPa versus 27.9 GPa). Likewise, there was an increase in the hardness of enamel (2.0 GPa versus 4.3 GPa) and dentin (0.5 GPa versus 0.7 GPa) with autoclaving. These changes suggested that the range of elastic modulus and hardness values previously reported in the literature may be partially due to the sterilization procedures. Treatment of the exterior of non-autoclaved teeth with Crest Whitestrips?, Opalescence? or UltraEtch? caused changes in the mechanical properties of both the enamel and dentin. Those treated with Crest Whitestrips? showed a reduction in the elastic modulus of enamel (55.3 GPa to 32.7 GPa) and increase in the elastic modulus of dentin (17.2 GPa to 24.3 GPa). Opalescence? treatments did not significantly affect the enamel properties, but did result in a decrease in the modulus of dentin (18.5 GPa to 15.1 GPa). Additionally, as expected, UltraEtch? treatment decreased the modulus and hardness of enamel (48.7 GPa to 38.0 GPa and 1.9 GPa to 1.5 GPa, respectively) and dentin (21.4 GPa to 15.0 GPa and 1.9 GPa to 1.5 GPa, respectively). Changes in the mechanical properties were linked to altered protein concentration within the tooth, as evidenced by fluorescence microscopy and Fourier transform infrared spectroscopy.     

A quantitative study of magnetization transfer in MAGIC gels

Magnetization transfer (MT) has been measured quantitatively as a function of radiation dose in MAGIC polymer gels. The MT rates between the free and immobile macromolecular proton pools (kmr and kfm), and the ratio of the sizes of these coupled proton pools (Pm/Pf), were measured by analysing the response to an inversion recovery sequence. While pm/pf increases linearly with dose, the fast MT rate kmf also increases with dose, unlike previous measurements in BANG gels. This dependence of kmf on dose suggests there are additional factors that modify spin exchange in MAGIC gels as irradiation occurs.     

Expression of podoplanin in the mouse tooth germ and apical bud cells

This study was designed to investigate the distribution of cells expressing podoplanin in the mouse tooth bud. Podoplanin expression was detected in enamel epithelia of the cervical loop at cell-cell contacts strongly, and weakly on the loosely aggregated stellate reticulum in the center and the neighboring stratum intermedium. Odontoblasts exhibited intense podoplanin expression at the junction with predentin while no expression was detected in the enamel organ containing ameloblasts. These results suggest that proliferating inner and outer enamel epithelia express podoplanin but that the expression is suppressed in the differentiated epithelia containing ameloblasts. On the other hand the podoplanin expression occurs in the differentiating odontoblasts and the expression is sustained in differentiated odontoblasts, indicating that odontoblasts have the strong ability to express podoplanin. In cultured apical bud cells podoplanin was detected at cell-cell contacts. In real-time PCR analysis the amount of podoplanin mRNA of the apical buds was 2-fold compared with the amount of kidney used as a positive control. These findings indicate that apical bud cells have the strong ability to express the podoplanin gene. Podoplanin is a mucin-type glycoprotein negatively charged by extensive O-glycosylation and a high content of sialic acid, which expresses the adhesive property. The podoplanin may contribute to form odontoblastic fiber or function as the anchorage to the tooth development and in proliferating epithelial cells of cervical loop and apical bud.     

Influence of environment on the mechanical behaviour of mature human enamel

OBJECTIVES: To investigate the role of different environments in regulating the mechanical behaviour of mature human enamel. METHODS: Healthy enamel samples were subjected to different environmental treatments such as ethanol dehydration, water re-hydration, desiccation at room temperature, and after heating (burnt) to 300 degrees C. Nanoindentation tests were done on all samples for determination of elastic modulus, hardness and indentation creep behaviour. Scanning electron microscopy (SEM) was used to observe surfaces and indentation impressions of different treated samples. RESULTS: Statistically significant differences of the mechanical properties were found following the various treatments. Burnt sample had the highest elastic modulus and hardness of approximately 115 and approximately 6 GPa, respectively, while the re-hydrated sample showed the lowest values of approximately 95 and approximately 4 GPa. The creep deformation showed the inverse response to the environment-induced elastic modulus results with negligible creep found for the burnt specimens. SEM showed that, although no significant structural changes were found for burnt samples after heating, there was much more cracking about the residual indentation impression. CONCLUSIONS: Because of the chemical and thermal stability of hydroxyapatite under the experimental conditions investigated, differences of mechanical behaviour of enamel are rationalized in terms of changes to the matrix proteins and loss of water within enamel. These results indicate that matrix proteins play an important role in regulating the mechanical behaviour of enamel as a biocomposite.     

On the critical parameters that regulate the deformation behaviour of tooth enamel

Tooth enamel is the hardest tissue in the human body with a complex hierarchical structure. Enamel hypomineralisation--a developmental defect--has been reported to cause a marked reduction in the mechanical properties of enamel and loss of dental function. We discover a distinctive difference in the inelastic deformation mechanism between sound and hypomineralised enamels that is apparently controlled by microstructural variation. For sound enamel, when subjected to mechanical forces the controlling deformation mechanism was distributed shearing within nanometre thick protein layer between its constituent mineral crystals; whereas for hypomineralised enamel microcracking and subsequent crack growth were more evident in its less densely packed microstructure. We develop a mechanical model that not only identifies the critical parameters, i.e., the thickness and shear properties of enamels, that regulate the mechanical behaviour of enamel, but also explains the degradation of hypomineralised enamel as manifested by its lower resistance to deformation and propensity for catastrophic failure. With support of experimental data, we conclude that for sound enamel an optimal microstructure has been developed that endows enamel with remarkable structural integrity for durable mechanical function.     

Effects of varying task constraints on solutions to joint coordination in a sit-to-stand task

The question of how multijoint movement is controlled can be studied by discovering how the variance of joint trajectories is structured in relation to important task-related variables. In a previous study of the sit-to-stand task, for instance, variations of body segment postures that leave the position of the body's center of mass (CM) unchanged were significantly greater than variations of body segment posture that varied the CM position. The present experiments tested the hypothesis that such structuring of joint configuration variability is accentuated when the mechanical or perceptual task demands are made more challenging. Six subjects performed the sit-to-stand task without vision (eyes closed), either on a normal or on a narrow support surface. An additional constraint on the postural task was introduced in a third condition by requiring subjects to maintain light touch (less than 1 N) with the fingertips while coming to a standing position on the narrow base of support. The joint configurations observed at each point in normalized time were analyzed with respect to trial-to-trial variability. The task variables CM and head position were used to define goal-equivalent sets of joint configurations ("uncontrolled manifolds," UCMs) within which variation of joint configuration leaves the task variables unchanged. The variability of joint configurations across trials was decomposed into components that did not affect (within the UCM) and that did affect (orthogonal to the UCM) the values of these task variables. Our results replicate the earlier finding of much larger variability in directions of joint space that leave the CM unchanged compared with directions that affect CM position. This effect was even more pronounced here than in the previous experiment, probably because of the more difficult perceptual conditions in the current study (eyes closed). When the mechanical difficulty of the task was increased, the difference between the two types of joint variability was further accentuated, primarily through increase in goal-equivalent variance. This provides evidence for the hypothesis that under challenging task constraints increased variability is selectively directed into task-irrelevant degrees of freedom. Because differential control along different directions of joint space requires coordination among joint angles, this observation supports the view that the CNS responds to increased task difficulty through enhanced coordination among degrees of freedom. The adaptive nature of this coordination is further illustrated by the similar enhanced use of goal-equivalent joint combinations to achieve a stable CM position when subjects stood up under the additional constraint of maintaining light touch with the fingertips. This was achieved by channeling goal-equivalent variability into different directions of joint configuration space.     

An immunocytochemical study of the routes of secretion of collagen and phosphophoryn from odontoblasts into dentin

Polyclonal antibodies to rat incisor phosphophoryns and to the amino-telopeptide of the alpha1 (I)-chain of type I collagen were used to follow the pathways of movement of collagen I (COL1) and phosphophoryns (PP) from synthesis in the odontoblast to secretion into the mineralized dentin. The antibodies were detected at the transmission electron microscopic level by their reaction with Protein A-colloidal gold conjugates. Special care was given in specimen preparation to retention of maximal antigenicity during fixation while maintaining cellular and extracellular ultrastructure at the mineralization front (MF) in nondemineralized sections. Intracellularly, COL1 and PP were detected within the endoplasmic reticulum (ER), the Golgi (G) and secretory granules (SG). However, as determined by double-immunolabeling with different size gold particles the COL1 and PP were not found together within the same ER, G or SG compartments. PP was localized within the tubular ER, round-shaped transitional vesicles, the Golgi and in narrow asymmetric SG. These asymmetric SG were found in abundance in the odontoblastic process. PP secretion from these vesicles was near the MF at the predentin-dentin boundary. COL1 was localized within rosette form ER compartments, the Golgi and in large, distinctive SG. COL1 was deposited at the cell-predentin boundary. No COL1 SG were seen within the odontoblastic process near the MF. In the region of the MF, prior to mineralization, the PP was localized along the surfaces of the COL1 fibrils of the predentin. The mineral phase etched surfaces revealed both COL1- and abundant mineral-associated PP. These data support the hypotheses that, in dentin, the interaction between COL1 and PP may initiate crystal nucleation and that additional interactions between PP and the growing crystals may modulate the crystal growth pattern and crystal size.     

HLA-A,B,C and DR antigens in Asaro speakers of Papua New Guinea

The HLA profile of the Asaro speakers of Papua New Guinea exhibits restricted polymorphisms. Antigens like AW24, MT1, and MB1 were present in almost every individual assayed. A CW6-related antigen and a DR locus antigen FT19 (a split of DRW6), not previously found in Pacific populations, were observed in a significant number of individuals. Ancestral HLA-B,C haplotypic combinations, such as B13, CW4 and BW60, CW3, were frequently found. Preliminary evidence is provided for an association between BW62 and CW6 in this population. The observed distributions of multiple-locus heterozygosities are similar to those expected under the null hypothesis of linkage equilibrium. The results indicate that the Asaro, among other highland populations, have been isolated long enough for pre-existing linkage disequilibria at recombinational distances of 0.8% or more (such as occur with HLA-A,B and HLA-B,DR haplotypes) to have broken down.