Evaluation of the presence or absence of papilla between tooth and implant

Objective: The purpose of this study was to evaluate the papilla level adjacent to single-tooth implants in the maxillary anterior region in individuals with cleft lip, alveolus, and palate to verify whether there is correlation among the vertical distance, horizontal distance, dental/prosthetic crown shape, and periodontal/peri-implant biotype with the presence of interproximal papilla. Design: Cross-sectional. Setting: Hospital for Rehabilitation of Craniofacial Anomalies, University of Sao Paulo (HRAC/USP). Patients: 77 papillae in 40 patients. Interventions: The periodontal/peri-implant biotype was clinically evaluated and characterized as thin or thick. Intraoral photographs were used to evaluate the presence or absence of papilla. Main Outcome Measures: Classification in scores (0 to 3) and determination of length (CL) and width (CW) of crowns adjacent to papillae. The CW/CL ratio was calculated for each crown in order to characterize it as square-shaped or triangular-shaped. The vertical and horizontal distances were obtained by radiographic evaluation. Results: The correlations between vertical distance and papilla score and horizontal distance and papilla score were statistically significant (p= .02 and p = .01). There was no significant difference between crown shape and periodontal/peri-implant biotype in distinct correlations with the papilla score (p = .41 and p = .07). Conclusion: The results suggest that the vertical and horizontal distances may have independent or combined relationship with the existence of interproximal papilla; the periodontal/peri-implant biotype (phenotype) was not correlated with the presence or absence of papilla, as well as the shape of the dental/prosthetic crown.

The dorsomedial visual areas in New World and Old World monkeys: homology and function

The extrastriate cortex near the dorsal midline has been described as part of an 'express' pathway that provides visual input to the premotor cortex. This pathway is considered important for the integration of sensory information about the visual field periphery and the skeletomotor system, especially in relation to the control of arm movements. However, a better understanding of the functional contributions of different parts of this complex has been hampered by the lack of data on the extent and boundaries of its constituent visual areas. Recent studies in macaques have provided the first detailed view of the topographical organization of this region in Old World monkeys. Despite differences in nomenclature, a comparison of the visuotopic organization, myeloarchitecture and connections of the relevant visual areas with those previously studied in New World monkeys reveals a remarkable degree of similarity and helps to clarify the subdivision of function between different areas of the dorsomedial complex. A caudal visual area, named DM or V6, appears to be important for the detection of coherent patterns of movement across wide regions of the visual field, such as those induced during self-motion. A rostral area, named M or V6A, is more directly involved with visuomotor integration. This area receives projections both from DM/V6 and from a separate motion analysis channel, centred on the middle temporal visual area (or V5), which detects the movement of objects in extrapersonal space. These results support the suggestion, made earlier on the basis of more fragmentary evidence, that the areas rostral to the second visual area in dorsal cortex are homologous in all simian primates. Moreover, they emphasize the importance of determining the anatomical organization of the cortex as a prerequisite for elucidating the function of different cortical areas.

The preparation of reach to grasp movements in adults with Down syndrome

The aim of this study was to determine the extent to which adults with Down syndrome (DS) are able to utilise advance information to prepare reach to grasp movements. The study comprised ten adults with DS; ten children matched to an individual in the group with DS on the basis of their intellectual ability, and twelve adult controls. The participants used their right hand to reach out and grasp illuminated perspex blocks. Four target blocks were positioned on a table surface, two to each side of the midsagittal plane. In the complete precue condition, participants were provided with information specifying the location of the target. In the partial precue condition, participants were given advance information indicating the location of the object relative to the midsagittal plane (left or right). In the null condition, advance information concerning the position of the target object was entirely ambiguous. It was found that both reaction times and movement times were greater for the participants with DS than for the adults without DS. The reaction times exhibited by individuals with DS in the complete precue condition were lower than those observed in the null condition, indicating that they had utilised advance information to prepare their movements. In the group with DS, when advance information specified only the location of the target object relative to the midline, reaction times were equivalent to those obtained when ambiguous information was given. In contrast, the adults without DS exhibited reaction times that were lower in both the complete and partial precue conditions when compared to the null condition. The pattern of results exhibited by the children was similar to that of the adults without DS. The movement times exhibited by all groups were not influenced by the precue condition. In summary, our findings indicate that individuals with DS are able to use advance information if it specifies precisely the location of the target object in order to prepare a reach to grasp movement. The group with DS were unable, however, to obtain the normal advantage of advance information specifying only one dimension of the movement goal (i.e., the position of an object relative to the body midline). (C) 2001 Elsevier Science B.V. All rights reserved.

Overexpression of a Slit homologue impairs convergent extension of the mesoderm and causes cyclopia in embryonic zebrafish

Slit is expressed in the midline of the central nervous system both in vertebrates and invertebrates. In Drosophila, it is the midline repellent acting as a ligand for the Roundabout (Robo) protein, the repulsive receptor which is expressed on the growth cones of the commissural neurons. We have isolated cDNA fragments of the zebrafish slit2 and slit3 homologues and found that both genes start to be expressed by the midgastrula stage well before the axonogenesis begins in the nervous system, both in the axial mesoderm, and slit2 in the anterior margin of the neural plate and slit3 in the polster at the anterior end of the prechordal mesoderm. Later, expression of slit2 mRNA is detected mainly in midline structures such as the floor plate cells and the hypochord, and in the anterior margins of the neural plates in the zebrafish embryo, while slit3 expression is observed in the anterior margin of the prechordal plate, the floorplate cells in the hindbrain, and the motor neurons both in the hindbrain and the spinal cord. To study the role of Slit in early embryos, we overexpressed Slit2 in the whole embryos either by injection of its mRNA into one-cell stage embryos or by heat-shock treatment of the transgenic embryos which carries the slit2 gene under control of the heat-shock promoter. Overexpression of Slit2 in such ways impaired the convergent extension movement of the mesoderm and the rostral migration of the cells in the dorsal diencephalon and resulted in cyclopia. Our results shed light on a novel aspect of Slit function as a regulatory factor of mesodermal cell movement during gastrulation. (C) 2001 Academic Press.

Dual trafficking of Slit3 to mitochondria and cell surface demonstrates novel localization for Slit protein

Drosophila slit is a secreted protein involved in midline patterning. Three vertebrate orthologs of the fly slit gene, Slit1, 2, and 3, have been isolated. Each displays overlapping, but distinct, patterns of expression in the developing vertebrate central nervous system, implying conservation of function. However, vertebrate Slit genes are also expressed in nonneuronal tissues where their cellular locations and functions are unknown. In this study, we characterized the cellular distribution and processing of mammalian Slit3 gene product, the least evolutionarily conserved of the vertebrate Slit genes, in kidney epithelial cells, using both cellular fractionation and immunolabeling. Slit3, but not Slit2, was predominantly localized within the mitochondria. This localization was confirmed using immunoelectron microscopy in cell lines and in mouse kidney proximal tubule cells. In confluent epithelial monolayers, Slit3 was also transported to the cell surface. However, we found no evidence of Slit3 proteolytic processing similar to that seen for Slit2. We demonstrated that Slit3 contains an NH2-terminal mitochondrial localization signal that can direct a reporter green fluorescent protein to the mitochondria. The equivalent region from Slit1 cannot elicit mitochondrial targeting. We conclude that Slit3 protein is targeted to and localized at two distinct sites within epithelial cells: the mitochondria, and then, in more confluent cells, the cell surface. Targeting to both locations is driven by specific NH2-terminal sequences. This is the first examination of Slit protein localization in nonneuronal cells, and this study implies that Slit3 has potentially unique functions not shared by other Slit proteins.

A case study of partial agenesis of the corpus callosum: Audiological implications

This case study represents four years of audiological observations, testing and aural habilitation of a female child with a partial agenesis of the corpus callosum (ACC). The ACC was diagnosed by MRI scans to eliminate neurological causes for developmental delay at six months of age. This child was also born with a cleft palate and was diagnosed with Robinow Syndrome at 3 years and 3 months of age. The audiological results showed an improvement in hearing thresholds over the four-year period. The child’s opthamologist also reported an improvement in visual skills over time. The most interesting aspect of the child’s hearing was the discrepancy between the monaural and the binaural results. That is, when assessed binaurally she often presented with a mild to moderate mixed loss and when assessed monaurally she showed a moderate to severe mixed loss for the right ear and a severe mixed loss for the left ear. This discrepancy between binaural and monaural results was evident for both aided and unaided tests. Parental reports of the child’s hearing were consistent with the binaural clinical results. This case indicates the need for audiologists to: (a) carefully monitor the hearing of children with ACC, (b) obtain monaural and binaural hearing and aided thresholds results, and (c) compare these children’s functional abilities to the objective test results obtained. This case does question whether hearing aids are appropriate for children with ACC. If hearing aids are deemed to be appropriate, then hearing aids with compression characteristics should be considered.

Development and reorganization of corticospinal projections in EphA4 deficient mice

The Eph family of receptor tyrosine kinases and their ligands, the ephrins, are important regulators of axon guidance and cell migration in the developing nervous system. Inactivation of the EphA4 gene results in axon guidance defects of the corticospinal tract, a major descending motor pathway that originates in the cortex and terminates at all levels of the spinal cord. In this investigation, we report that although the initial development of the corticospinal projection is normal through the cortex, internal capsule, cerebral peduncle, and medulla in the brain of EphA4 deficient animals, corticospinal axons exhibit gross abnormalities when they enter the gray matter of the spinal cord. Notably, many corticospinal axons fail to remain confined to one side of the spinal cord during development and instead, aberrantly project across the midline, terminating ipsilateral to their cells of origin. Given the possible repulsive interactions between EphA4 and one of its ligands, ephrinB3, this defect could be consistent with a loss of responsiveness by corticospinal axons to ephrinB3 that is expressed at the spinal cord midline. Furthermore, we show that EphA4 deficient animals exhibit ventral displacement of the mature corticospinal termination pattern, suggesting that developing corticospinal axons, which may also express ephrinB3, fail to be repelled from areas of high EphA4 expression in the intermediate zone of the normal spinal cord. Taken together, these results suggest that the dual expression of EphA4 on corticospinal axons and also within the surrounding gray matter is very important for the correct development and termination of the corticospinal projection within the spinal cord. J. Comp. Neurol. 436: 248-262, 2001. (C) 2001 Wiley-Liss, Inc.

A Case Study of Partial Agenesis of the Corpus Callosum: Audiological Implications

This case study presents four and a half years of audiological observations, testing and aural habilitation of a female child with a partial agenesis of the corpus callosum (ACC). The ACC was diagnosed by MRI scan performed at 6 months of age to eliminate neurological causes for the developmental delay. This child was also born with a cleft palate and was diagnosed with Robinow Syndrome at 3 years and 3 months of age. The audiological results showed an improvement in hearing thresholds over the 4-year period. The child’s ophthalmologist also reported an improvement in visual skills over time. The most interesting aspect of the child’s hearing was the discrepancy between the monaural and the binaural results. That is, when assessed binaurally she often presented with a mild to moderate mixed loss and, when assessed monaurally, she showed a moderate to severe mixed loss for the right ear and a severe mixed loss for the left ear. Over time, the discrepancy between the monaural and binaural results changed. When assessed binaurally, the loss decreased to normal low frequency hearing sloping to a mild high frequency loss. When assessed monaurally, the most recent results showed a mild loss for the right ear and a moderate loss for the left ear. This discrepancy between binaural and monaural results was evident for both aided and unaided tests. For the most recent thresholds, the binaural results were consistent with the right monaural thresholds for the first time over the four and a half years. Parental reports of the child’s hearing were consistent with the binaural clinical results. This case indicates the need for audiologists to (1) carefully monitor the hearing of children with ACC, (2) obtain monaural and binaural hearing and aided thresholds results, and (3) compare these children’s functional abilities with the objective test results obtained. This case does question whether hearing aids are appropriate for children with ACC. If hearing aids are deemed to be appropriate, then hearing aids with compression characteristics should be considered.

Expression and role of roundabout-1 in embryonic Xenopus forebrain

The receptor Roundabout-1 (Robo1) and its ligand Slit are known to influence axon guidance and central nervous system (CNS) patterning in both vertebrate and nonvertebrate systems. Although Robo-Slit interactions mediate axon guidance in the Drosophila CNS, their role in establishing the early axon scaffold in the embryonic vertebrate brain remains unclear. We report here the identification and expression of a Xenopus Robo1 orthologue that is highly homologous to mammalian Robo1. By using overexpression studies and immunohistochemical and in situ hybridization techniques, we have investigated the role of Robo1 in the development of a subset of neurons and axon tracts in the Xenopus forebrain. Robo1 is expressed in forebrain nuclei and in neuroepithelial cells underlying the main axon tracts. Misexpression of Robo1 led to aberrant development of axon tracts as well as the ectopic differentiation of forebrain neurons. These results implicate Robo1 in both neuronal differentiation and axon guidance in embryonic vertebrate forebrain. (C) 2002 Wiley-Liss, Inc.

N-terminal Slit2 promotes survival and neurite extension in cultured peripheral neurons

To investigate the effect of the N-terminal Slit2 protein on neuronal survival and development, recombinant human N-terminal Slit2 (N-Slit2) was assayed against isolated embryonic chick dorsal root ganglion sensory, ciliary ganglion and paravertebral sympathetic neurons. N-Slit2 promoted significant levels of neuronal survival and neurite extension in all of these populations. The protein was also assayed against postnatal mouse dorsal root ganglion neurons and found to promote neuronal survival in a similar manner. These findings suggest the Slit proteins may play an important role during development of the nervous system, mediating cellular survival in addition to the well documented role these proteins play in axonal and neuronal chemorepulsion.

The distribution and morphological characteristics of serotonergic cells in the brain of monotremes

The distribution and cellular morphology of serotonergic neurons in the brain of two species of monotremes are described. Three clusters of serotonergic neurons were found: a hypothalamic cluster, a cluster in the rostral brainstem and a cluster in the caudal brainstem. Those in the hypothalamus consisted of two groups, the periventricular hypothalamic organ and the infundibular recess, that were intimately associated with the ependymal wall of the third ventricle. Within the rostral brainstem cluster, three distinct divisions were found: the dorsal raphe nucleus (with four subdivisions), the median raphe nucleus and the cells of the supralemniscal region. The dorsal raphe was within and adjacent to the periaqueductal gray matter, the median raphe was associated with the midline ventral to the dorsal raphe, and the cells of the supralemniscal region were in the tegmentum lateral to the median raphe and ventral to the dorsal raphe. The caudal cluster consisted of three divisions: the raphe obscurus nucleus, the raphe pallidus nucleus and the raphe magnus nucleus. The raphe obscurus nucleus was associated with the dorsal midline at the caudal-most part of the medulla oblongata. The raphe pallidus nucleus was found at the ventral midline of the medulla around the inferior olive. Raphe magnus was associated with the midline of the medulla and was found rostral to both the raphe obscurus and raphe pallidus. The results of our study are compared in an evolutionary context with those reported for other mammals and reptiles. Copyright (C) 2002 S. Karger AG, Basel.

The embryonic development of the bodywall and nervous system of the cestode flatworm Hymenolepis diminuta

Cestodes (tapeworms) are a derived, parasitic clade of the phylum Platyhelminthes (flatworms). The cestode body wall represents an adaptation to its endoparasitic lifestyle. The epidermis forms a nonciliated syncytium, and both muscular and nervous system are reduced. Morphological differences between cestodes and free-living flatworms become apparent already during early embryogenesis. Cestodes have a complex life cycle that begins with an infectious larva, called the oncosphere. In regard to cell number, cestode oncospheres are among the simplest multicellular organisms, containing in the order of 50-100 cells. As part of our continuing effort to analyze embryonic development in flatworms, we describe here the staining pattern obtained with acTub in embryos and larvae of the cestode Hymenolepis diminuta and, briefly, the monogenean Neoheterocotyle rhinobatidis. In addition, we labeled the embryonic musculature of Hymenolepis with phalloidin. In Hymenolepis embryos, two different cell types that we interpret as neurons and epidermal gland cells express acTub. There exist only two neurons that develop close to the midline at the anterior pole of the embryo. The axons of these two neurons project posteriorly into the center of the oncosphere, where they innervate the complex of muscles that is attached to the booklets. In addition to neurons, acTub labels a small and invariant set of epidermal gland cells that develop at superficial positions, anteriorly adjacent to the neurons, in the dorsal midline, and around the posteriorly located hooklets. During late stages of embryogenesis they spread and form a complete covering of the embryo. We discuss these data in the broader context of platyhelminth embryology.

Promiscuous CTL recognition of viral epitopes on multiple human leukocyte antigens: Biological validation of the proposed HLA A24 supertype

Multiple HLA class I alleles can bind peptides with common sequence motifs due to structural similarities in the peptide binding cleft, and these groups of alleles have been classified into supertypes. Nine major HLA supertypes have been proposed, including an A24 supertype that includes A*2301, A*2402, and A*3001. Evidence for this A24 supertype is limited to HLA sequence homology and/or similarity in peptide binding motifs for the alleles. To investigate the immunological relevance of this proposed supertype, we have examined two viral epitopes (from EBV and CMV) initially defined as HLA-A*2301-binding peptides. The data clearly demonstrate that each peptide could be recognized by CTL clones in the context of A*2301 or A*2402; thus validating the inclusion of these three alleles within an A24 supertype. Furthermore, CTL responses to the EBV epitope were detectable in both A*2301(+) and A*2402(+) individuals who had been previously exposed to this virus. These data substantiate the biological relevance of the A24 supertype, and the identification of viral epitopes with the capacity to bind promiscuously across this supertype could aid efforts to develop CTL-based vaccines or immunotherapy. The degeneracy in HLA restriction displayed by some T cells in this study also suggests that the dogma of self-MHC restriction needs some refinement to accommodate foreign peptide recognition in the context of multiple supertype alleles.

Trichostome ciliates from Australian marsupials. III. Megavestibulum gen. nov. (Litostomatea : Macropodiniidae)

A new macropodiniid ciliate genus, Megavestibulum, is described which is endocommensal in the stomach of macropodid marsupials. Two new species, M. morganorum and M. kuhri, are described from Macropus dorsalis and Wallabia, bicolor respectively. Megavestibulum is holotrichous, the somatic ciliation arranged into meridional, curving kineties between broad ridges. The interkinetal ridges are lined apically by thick-walled vacuoles similar to those lining the longitudinal grooves of Macropodinium. The conical vestibulum is apical and very large, occupying up to 1/3 of the cell volume. The vestibular lip appears closable and has a cleft which may allow distention of the vestibullum to ingest large food items. The vestibular ultrastructure is similar to that of Macropodinium including the presence of vestibular vacuoles and the hemispherical differentiation of the distribution of small nematodesmata. Many specimens contained ingested whole ciliates of the genera Amylovorax and Polycosta. The structure of the vestibulum suggests that Megavestibulum is adapted for life as an active predator of other stomach ciliates as well as sweeping in small particulates. The morphology of Megavestibulum suggests that it represents the plesiomorphic body plan within the family Macropodiniidae.

The AF-1 Domain of the Orphan Nuclear Receptor NOR-1 Mediates Trans-activation, Coactivator Recruitment, and Activation by the Purine Anti-metabolite 6-Mercaptopurine

NOR-1/NR4A3 is an orphan member of the nuclear hormone receptor superfamily. NOR-1 and its close relatives Nurr1 and Nur77 are members of the NR4A subgroup of nuclear receptors. Members of the NR4A subgroup are induced through multiple signal transduction pathways. They have been implicated in cell proliferation, differentiation, T-cell apoptosis, chondrosarcomas, neurological disorders, inflammation, and atherogenesis. However, the mechanism of transcriptional activation, coactivator recruitment, and agonist-mediated activation remain obscure. Hence, we examined the molecular basis of NOR-1-mediated activation. We observed that NOR-1 trans-activates gene expression in a cell- and target-specific manner; moreover, it operates in an activation function (AF)-1-dependent manner. The N-terminal AF-1 domain delimited to between amino acids 1 and 112, preferentially recruits the steroid receptor coactivator (SRC). Furthermore, SRC-2 modulates the activity of the AF-1 domain but not the C-terminal ligand binding domain (LBD). Homology modeling indicated that the NOR-1 LBD was substantially different from that of hRORbeta, a closely related AF-2-dependent receptor. In particular, the hydrophobic cleft characteristic of nuclear receptors was replaced with a very hydrophilic surface with a distinct topology. This observation may account for the inability of this nuclear receptor LBD to efficiently mediate cofactor recruitment and transcriptional activation. In contrast, the N-terminal AF-1 is necessary for cofactor recruitment and can independently conscript coactivators. Finally, we demonstrate that the purine anti-metabolite 6-mercaptopurine, a widely used antineoplastic and anti-inflammatory drug, activates NOR-1 in an AF-1-dependent manner. Additional 6-mercaptopurine analogs all efficiently activated NOR-1, suggesting that the signaling pathways that modulate proliferation via inhibition of de novo purine and/or nucleic acid biosynthesis are involved in the regulation NR4A activity. We hypothesize that the NR4A subgroup mediates the genotoxic stress response and suggest that this subgroup may function as sensors that respond to genotoxicity.