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PubMed2003

Somatosensory organization and behavior in naked mole-rats: II. Peripheral structures, innervation, and selective lack of neuropeptides associated with thermoregulation and pain.

African naked mole-rats are subterranean rodents that have a robust orienting response to stimulation of unique vibrissa-like body hairs that are widely spaced over an otherwise hairless skin. To determine whether these large body hairs have a specialized organization similar to facial vibrissae, the structure and innervation of facial vibrissa follicles, body hair follicles, and intervening skin in naked mole-rats was compared with that in rats and a furred African mole-rat species (the common mole-rat). Immunofluorescence and lectin-binding analyses revealed that the body hair follicles in naked mole-rats were exceptionally large and well innervated, similar to guard hairs of furred species. However, these body vibrissae lacked the anatomic specializations and unique types of innervation affiliated with follicle sinus complexes of facial vibrissae. In contrast to the furred species, naked mole-rats had a paucity of Abeta-fiber Merkel endings at all peripheral locations. Naked mole-rats also were completely lacking in cutaneous C-fibers immunoreactive for substance P and calcitonin gene-related peptide. In contrast, the hairless skin of the naked mole-rats had an exceptional abundance of presumptive Adelta-fibers. The unusual features of the cutaneous innervation in naked mole-rats are presumably adaptations to their subterranean environment and that they are the only known poikilothermic mammal. The features of this mammalian model system provide unique opportunities to discriminate mechanisms related to tactile spatial orientation, vascular regulation, and nociception.

Afferent Pathways↗

PubMed1994

Rat posterior parietal cortex: topography of corticocortical and thalamic connections.

Anatomical and functional findings support the contention that there is a distinct posterior parietal cortical area (PPC) in the rat, situated between the rostrally adjacent hindlimb sensorimotor area and the caudally adjacent secondary visual areas. The PPC is distinguished from these areas by receiving thalamic afferents from the lateral dorsal (LD), lateral posterior (LP), and posterior (Po) nuclei, in the absence of input from the ventrobasal complex (VB) or dorsal lateral geniculate (DLG) nuclei. Behavioral studies have demonstrated that PPC is involved in spatial orientation and directed attention. In the present study we used fluorescent retrograde axonal tracers primarily to investigate the cortical connections of PPC, in order to determine the organization of the circuitry by which PPC is likely to participate in these functions, and also to determine how the topography of its thalamic connections differs from that of neighboring cortical areas. The cortical connections of PPC involve the ventrolateral (VLO) and medial (MO) orbital areas, medial agranular cortex (area Fr2), portions of somatic sensory areas Par1 and Par2, secondary visual areas Oc2M and Oc2L, auditory area Te1, and retrosplenial cortex. The secondary visual areas Oc2L and Oc2M have cortical connections which are similar to those of PPC, but are restricted within orbital cortex to area VLO, and within area Fr2 to its caudal portion, and do not involve auditory area Te1. The cortical connections of hindlimb cortex are largely restricted to somatic sensory and motor areas. Retrosplenial cortex, which is medially adjacent to PPC, has cortical connections that are prominent with visual cortex, do not involve somatic sensory or auditory cortex, and include the presubiculum. We conclude that PPC is distinguished by its pattern of cortical connections with the somatic sensory, auditory and visual areas, and with areas Fr2, and VLO/MO, in addition to its exclusive thalamic connectivity with LD, LP and Po. Because recent behavioral studies indicate that PPC, Fr2 and VLO are involved in directed attention and spatial learning, we suggest that the interconnections among these three cortical areas represent a major component of the circuitry for these functions in rats.

Animals↗

PubMed1997

Interaction of human CYP17 (P-450(17alpha), 17alpha-hydroxylase-17,20-lyase) with cytochrome b5: importance of the orientation of the hydrophobic domain of cytochrome b5.

Human CYP17 (P-450(17alpha), 17alpha-hydroxylase-17,20-lyase)-catalysed side-chain cleavage of 17alpha-hydroxyprogestogens into androgens is greatly dependent on the presence of cytochrome b5. The native form of cytochrome b5 is composed of a globular core, residues 1-98, followed by a membrane insertable C-terminal tail, residues 99-133. In the present study the abilities of five different forms of cytochrome b5 to support the side-chain cleavage activity of CYP17 were compared. The five derivatives were: the native pig cytochrome b5 (native pig), its genetically engineered rat counterpart (core-tail), the soluble core form of the latter (core), the core with the secretory signal sequence of alkaline phosphatase appended to its N-terminal (signal-core) and the latter containing the C-terminal tail of the native rat protein (signal-core-tail). When examined by Edman degradation and MS, the engineered proteins were shown to have the expected N-terminal amino acid sequences and molecular masses. The native pig was found to be acetylated at the N-terminal. The native pig and core-tail enzymes were equally efficient at enhancing the side-chain cleavage activity of human CYP17 and the signal-core-tail was 55% as efficient. The core and signal-core constructs were completely inactive in the aforementioned reaction. All the five derivatives were reduced to varying degrees by NADPH:cytochrome P-450 (NADPH-P450) reductase and the relative efficiencies of this reduction were reminiscent of the behaviour of these derivatives in supporting the side-chain cleavage reaction. In the side-chain cleavage assay, however, NADPH-P450 reductase was used in large excess so that the reduction of cytochrome b5 derivatives was not rate-limiting. The results highlight that productive interaction between cytochrome b5 and CYP17 is governed not only by the presence of a membrane insertable hydrophobic region on the cytochrome b5 but also by its defined spatial orientation at the C-terminal.

Acetaldehyde↗

PubMed2002

Chirotopical properties of cisoid enones from circular dichroism (CD) and anisotropic circular dichroism (ACD) spectroscopy.

Substituted cisoid 4-en-6-one steroids with isotropically distributed and partially oriented molecules were analyzed by circular dichroism (CD) and anisotropic circular dichroism (ACD) spectroscopy, respectively. CD and ACD data supplement their respective phenomenological information. For a series of C3-substituted enones 1 to 7, the difference of CD (Delta epsilon) and ACD (Delta epsilon(A)) values, that is, Delta epsilon -Delta epsilon(A), vary in the n-* transition region in the same direction, independently of the nature and position (3 alpha or 3 beta) of the substituent. For 7-bromo-substituted enones 5 and 6 the sign of the n-pi* CD band is opposite to that predicted by the enone helicity rule. The ACD data indicate that this behavior is a consequence of the effect of vibronic coupling caused by the 7-bromo substituent. In contrast to the results obtained for the series of C7-unsubstituted compounds 1 to 4, the intensity of the CD bands for 5 and 6 is determined by the vibrational progressions of a different symmetry. Therefore, the helicity rule must fail in both cases because the rule can only be applied to those vibrational transitions for which the rule was developed. The sign of the coordinates Delta epsilon(*)(II), estimated from the ACD data, yields additional stereochemical information that cannot be obtained from the CD data alone. The CD and ACD spectra in the region of the pi-pi* transition vary for enones 1 to 4 in a different fashion and indicate dependence upon spatial orientation (3 alpha or 3 beta) of substituents. This dependence may lead to the possibility of extracting additional stereochemical information from the ACD spectra. Furthermore, the experimental findings indicate that the second CD band located at about 220 nm belongs to a forbidden transition and not to an allowed pi-pi* transition.

Journal Article↗

PubMed2003

Restoration of high-level transport activity by human reduced folate carrier/ThTr1 thiamine transporter chimaeras: role of the transmembrane domain 6/7 linker region in reduced folate carrier function.

The reduced folate carrier (RFC; SLC19A1) is closely related to the thiamine transporter, SLC19A2 (ThTr1). Hydropathy models for these homologous transporters predict up to 12 transmembrane domains (TMDs), with internally oriented N- and C-termini and a large central loop between TMDs 6 and 7. The homologies are localized mostly in the TMDs. However, there is little similarity in their N- and C-terminal domains and the central peptide linkers connecting putative TMDs 1-6 and TMDs 7-12. To explore the functional role of the 61-amino acid central linker in the human RFC (hRFC), we introduced deletions of 49 and 60 amino acids into this region, differing by the presence of a stretch of 11 highly conserved amino acids between the human and rodent RFCs (positions 204-214). An additional hRFC construct was prepared in which only the 11 conserved amino acids were deleted. The resulting hRFC(D215-R263 Delta), hRFC(K204-R263 Delta) and hRFC(K204-R214 Delta) proteins were transfected into transport-impaired K562 cells. The deletion constructs were all expressed in plasma membranes; however, they were completely inactive for methotrexate and (6 S )5-formyl tetrahydrofolate transport. Insertion of non-homologous 73- and 84-amino acid fragments from the structurally analogous ThTr1 linker region into position 204 of hRFC(K204-R263 Delta) restored low levels of transport (16-21% of the wild type). Insertion of the ThTr1 linkers into hRFC(D215-R263 Delta) at position 215 restored 60-80% of wild-type levels of transport. Collectively, our results suggest that the role of the hRFC linker peptide is to provide the proper spatial orientation between the two halves of the hRFC protein for optimal function, and that this is largely independent of amino acid sequence. Our results also demonstrate a critical transport role for the stretch of 11 conserved amino acids starting at position 204 of hRFC.

Amino Acid Sequence↗

PubMed2003

Determinants of competency judgments by experienced laparoscopic surgeons.

BACKGROUND: The definitive criteria for assessing competence remain elusive. In our study, we aimed to identify the determinants of competence assessment used by individual laparoscopic surgeons. METHODS: In a blinded fashion, five laparoscopic surgeons rated 27 subjects on three laparoscopic simulations in four skill categories: clinical judgment, dexterity, serial/simultaneous complexity, and spatial orientation. The raters then assessed overall subject competence for each procedure. Point-biserial correlational analyses and cluster analyses were performed to ascertain the relationships among the various scales. RESULTS: All of the correlations between the skills' ratings and competence judgments were statistically significant ( p <.05). No skill rating was consistently more highly correlated with the competence rating. There were no distinct patterns of correlations for each rater or each procedure. One factor emerged from each cluster analysis of the skills measures. CONCLUSIONS: The results suggest that the four skills scored in the study are highly correlated with each other and are important in determining competence. The cluster analyses revealed that the surgeon raters shared a common perception of competence.

Adult↗

PubMed2005

Spatial- versus object-oriented architectural environments: preference and perception.

This study examined changes in perceptual response and preference a specific category of architectural environment by age groups. Understanding relationships among age, perception, and preference is important in creating more appropriate environments. The hypothesis was that individuals who score field-dependent on an Embedded Figures Test would prefer architectural environments which support spatial orientation, while individuals who are field-independent would prefer environments without information on spatial organization or an object-oriented space. It was also hypothesized that children and elderly persons would score more field-dependent and prefer spatially orienting spaces. 64 subjects ages 4 to 85 years were recruited from local schools, various organizations for seniors and adults, given the Embedded Figures Test to measure field dependence, and were compared. Their scores were compared by preference for one of the two environments. Hypotheses were not supported for the spaces overall, however, clear patterns regarding seating preference were identified. Children and seniors had significantly more field-dependent preferences.

Adolescent↗

PubMed2003

Can we help persons with dementia find their way in a new environment?

The objective of this study was to conduct a randomized controlled trial to examine the effects of a way-finding intervention on residents' ability to find their way in a new environment. The effect of the intervention on the residents' spatial orientation and agitation were also examined. The study was conducted on four nursing home units in a geriatric center and the final sample consisted of 32 residents with Alzheimer's disease (17 in the treatment group and 15 in the control group). The intervention consisted of the use of a location map and a behavioral training technique, which was provided to residents over the course of a month. Repeated measures analysis of variance and McNemar tests were used to compare the groups in regard to changes in the outcomes over time. Results indicated that the residents' in the treatment group demonstrated an increased ability to find their way to the dining room one week after the intervention. The intervention effect was not sustained three months later.

Activities of Daily Living↗

PubMed2005

Manual tracking in three dimensions.

Little is known about the manual tracking of targets that move in three dimensions. In the present study, human subjects followed, with the tip of a hand-held pen, a virtual target moving four times (period 5 s) around a novel, unseen path. Two basic types of target paths were used: a peanut-shaped Cassini ellipse and a quasi-spherical shape where four connected semicircles lay in orthogonal planes. The quasi-spherical shape was presented in three different sizes, and the Cassini shape was varied in spatial orientation and by folding it along one of the three bend axes. During the first cycle of Cassini shapes, the hand lagged behind the target by about 150 ms on average, which decreased to 100 ms during the last three cycles. Tracking performance gradually improved during the first 3 s of the first cycle and then stabilized. Tracking was especially good during the smooth, planar sections of the shapes, and time lag was significantly shorter when the tracking of a low-frequency component was compared to performance at a higher frequency (-88 ms at 0.2 Hz vs. -101 ms at 0.6 Hz). Even after the appropriate adjustment of the virtual target path to a virtual shape tracing condition, tracking in depth was poor compared to tracking in the frontal plane, resulting in a flattening of the hand path. In contrast to previous studies where target trajectories were linear or sinusoidal, these complex trajectories may have involved estimation of the overall shape, as well as prediction of target velocity.

Feedback↗

PubMed2005

Independent binocular integration for form and colour.

Although different features of an object are processed in anatomically distinct regions of the cerebral cortex, they often appear bound together in perception. Here, using binocular rivalry, we reveal that the awareness of form can occur independently from the awareness of colour. First, we report that, if both eyes briefly view a grating stimulus prior to the presentation of the same grating in one eye and an orthogonal grating in the other, subjects tend to report perceptual dominance of the non-primed grating. The primer was most effective when it was similar in orientation, spatial frequency and spatial phase to one of the rival images. Next, we showed that the process underlying the binocular integration of chromatic information was selectively influenced by the colour of a previously presented stimulus. We then combined these paradigms by using a primer that had the same colour as one rival stimulus, but the same form as the other stimulus. In this situation, we found that rival stimuli differing in form and colour can sometimes achieve states of dominance in which the chromatic information from one eye's image combines with the form of the other eye's image temporarily creating a binocular impression that corresponds with neither monocular component. Finally, we demonstrated that during continuous viewing of rival stimuli differing in form and colour, chromatic integration could occur independently of form rivalry. Paradoxically, however, we found that changes to the form of the stimulus had more of an influence on chromatic integration than on form rivalry. Together these phenomena show that the neural processes involved in integrating information from the two eyes can operate selectively on different stimulus features.

Color Perception↗

PubMed1986

Disturbances in exploratory behavior and functional recovery in the Y and radial mazes following dopamine depletion of the lateral septum.

The effects of 6-hydroxydopamine (6-OHDA) injected into the lateral septum in rats were investigated for spontaneous alternation behavior in a Y maze and for spatially oriented behavior in an 8-arm radial maze. The performance of the animals in these tests was assessed under two physiological states, food-satiated and food-deprived. The selective depletion of septal dopaminergic concentrations leads to behavioral disturbances in both the Y and the radial mazes. These deficits disappeared when the animals with 6-OHDA lesions were food-deprived. These results confirm other studies from our laboratory and support two conclusions. First, lesions of dopaminergic neurons lead to behavioral impairments which resemble those found after the total lesion of the structure they innervate. Second, these behavioral impairments are responsive to therapeutic treatments, manipulations of the internal or external environment, or the level of arousal, since under certain conditions a recovery of function can occur in the absence of dopaminergic neurons. These two points provide additional support for a nonspecific role for the dopaminergic neurons originating in the ventral tegmental area. These neurons could have a permissive role in the functioning of the forebrain structures they innervate.

Animals↗

PubMed2002

A study of the ultrastructure and staining characteristics of the 'dental star' of equine incisors.

The objective of this study was to examine the diameter, extent, orientation and contents of dentinal tubules in order to validate the hypothesis of pigment penetration into the dental star of equine incisival occlusal surfaces. The time of appearance and the configuration of the dental star on the incisival occlusal surface are macroscopically visible features that, along with other more reliable parameters, are used for the determination of horses' age. Although dental stars are an integral part of the equine incisor occlusive surface, the exact nature and microstructure of the dental star are poorly documented. Therefore, equine incisor dentine was examined macroscopically and by scanning electron microscopy to elucidate numerical density, diameter and 3-dimensional organisation of the dentinal tubules in the dental star. The dental star is surrounded by primary dentine and consists of a central core of tertiary dentine, an intermediate ring of pale secondary dentine and a peripheral rim of darker, yellowish-brown secondary dentine. The central core of tertiary dentine contains relatively few dentinal tubules (<8000/mm2) that have small diameters (mean +/- s.d. 1.67 +/- 034 microm) and are arranged in an irregular pattern. The surrounding pale ring of secondary dentine comprises manifestly more and wider tubules that lie almost parallel to the occlusal surface. The dark peripheral rim of the dental star contains high numbers of tubules (28,000-58,000/mm2) that have wide luminal diameters (mean +/- s.d. 3.09 +/- 0.31 microm) and open perpendicular to the occlusal surface. In contrast, the primary dentine surrounding the dental star is made up by a lower number of dentinal tubules (<25,000/mm2). The tubules of primary dentine, which are initially mean +/- s.d. 5.15 +/- 0.80 microm wide, are narrowed by circumferential deposits of peritubular dentine and are obliquely exposed at the occlusal surface. From these observations, it was concluded that the regional differences in numerical density, diameter and spatial orientation of the dentinal tubules may influence the penetration of food pigments into the equine occlusal surface and result in the particular staining of the dental star.

Age Determination by Teeth↗

PubMed2005

The influence of exploration mode, orientation, and configuration on the haptic Müller-Lyer illusion.

We studied the impact of manner of exploration, orientation, spatial position, and configuration on the haptic Müller-Lyer illusion. Blindfolded sighted subjects felt raised-line Müller-Lyer and control stimuli. The stimuli were felt by tracing with the index finger, free exploration, grasping with the index finger and thumb, or by measuring with the use of any two or more fingers. For haptic judgments of extent a sliding tangible ruler was used. The illusion was present in all exploration conditions, with overestimation of the wings-out compared to wings-in stimuli. Tracing with the index finger reduced the magnitude of the illusion. However, tracing and grasping induced an overall underestimation of size. The illusion was greatly attenuated when stimuli were felt with the index fingers of both hands. Illusory misperception was not altered by the position in space of the Müller-Lyer stimuli. No effects of changes in the thickness of the line shaft were found, but there were effects of the length of the wing endings for the smaller, 5.1 cm stimuli. The theoretical and practical implications of the results are discussed.

Analysis of Variance↗

PubMed1989

Visual search: spatial frequency and orientation.

Observers searched for a Gaussian-windowed patch of sinewave grating (Gabor pattern) through displays containing varying numbers of other such patterns (distractors). When the spatial frequencies of target and distractors differed by +/- 2 octaves and their orientations by +/- 60 degrees, the search proceeded spatially in parallel irrespective of whether the target could be discriminated in terms of spatial frequency differences alone, orientation differences alone, or their combination. However, when target and distractors differed by only +/- .5 octave in spatial frequency and by +/- 15 degrees in orientation, the search was serial and self-terminating, again irrespective of the nature of the target-distractor differences. These findings show that, contrary to some suggestions, the preattentive detection of targets defined by conjunctions of spatial frequency and orientation may occur, but only when the spectral distance between target and distractors allows their encoding by independent mechanisms.

Adult↗

PubMed2007

Head position of helicopter pilots during slalom maneuvers.

INTRODUCTION: Pilots typically tilt their heads when executing coordinated banking turns, a phenomenon commonly attributed to the putative opto-kinetic cervical reflex (OKCR). The OKCR is usually described as a reflex, primarily driven by stimuli in the visual periphery, and is important to a pilot's spatial orientation by providing a relatively stabilized horizontal frame of reference. The present paper presents an alternative hypothesis for the observed head tilting seen in pilots. METHODS: An archived data set, originally collected for other purposes, contained the head turn, pitch, and tilt of 4 helicopter pilots recorded at 10 Hz as the pilots executed 42 slalom maneuvers in an AH Mk 7 Lynx helicopter under visual flight conditions. The analytic method was a correlational analysis of head turn, pitch, and tilt. RESULTS: As expected, pilots routinely tilted their heads during the slaloms in a fashion typically attributed to the OKCR. Correlations among head turn, tilt, and pitch showed that when the helicopter turned left, the head, presumably to look into the turn, turned left and also pitched up and tilted right. Similarly, when the helicopter turned right, the head, presumably to look into the turn, turned right, pitched up, and tilted left. CONCLUSIONS: The head tilting usually attributed to a neuromuscular reflex driven by visual stimuli may be a biomechanical consequence of the head posture pilots assume when they simply look where they are going, eliminating the need to postulate the existence of a novel neuromuscular reflex.

Adult↗

PubMed2005

Purkinje cell loss affects differentially the execution, acquisition and prepulse inhibition of skeletal and facial motor responses in Lurcher mice.

Adult heterozygous Lurcher mice show a degeneration of almost all Purkinje cells and 90% of the granular cells of the cerebellum, resulting in ataxia or general deficits in motor coordination. These mice are therefore an excellent model for studying the role of the cerebellar cortex in motor performance, including the acquisition of new motor abilities. The performance of 3-month-old Lurcher mice was studied in various behavioural (fall, horizontal bar, rotating cylinder, and ladder), spatial orientation (water maze) and associative learning (eyelid classical conditioning) tasks and compared with that of wild-type mice. Behavioural tasks indicated a deficit for motor abilities in Lurcher mice but with some adaptation to the tests and improvement in performance. Wild-type and Lurcher mice performed swimming equally, but the latter learned the task significantly more slowly than the former. The late component of reflex blinks was smaller in amplitude and had a longer latency in Lurcher mice than in controls. Learning curves for Lurcher mice during classical conditioning of eyelid responses were similar to controls, but the amplitude of the learned response in Lurcher mice was significantly lower. The startle response to a severe tone was similar in both control and Lurcher mice but the latter were unable to produce prepulse inhibition. These results suggest that the cerebellar cortex is not indispensable for the performance of this complete set of skeletal and facial tasks, or for the acquisition of new motor abilities, but it is for the appropriate execution and adjustment of any of these motor activities.

Acoustic Stimulation↗

PubMed2004

Feature synergy depends on feature contrast and objecthood.

Pairs of texture figures, defined by contrast in spatial frequency, orientation or both cues (redundant texture definition) had to be detected within a homogeneous Gabor field. In line with expectation we find better detection performance for arrangements with higher feature contrast along the border where the figures abut. Redundantly defined figures show synergy, a significant performance increase compared to the prediction of independent processing of orientation and spatial frequency cues. As found in previous studies [Spatial Vision 16 (2003) 459; Vision Research (submitted for publication)] this performance advantage is negatively correlated with visibility. In particular, figures with high border feature contrast are easily detectable but show weak synergy whereas figures with low border feature contrast are barely detectable but remarkably benefit from redundant texture definition. Closer analysis reveals that the form of the figures is also crucial: As long as they maintain a clear two dimensional shape the synergy effect is only marginally affected by variation figure size and border length. But when they degrade to one dimensional Gabor element arrays, synergy almost completely vanishes. The results imply that both factors, low visibility and objecthood, are critical for feature synergy. We conclude that facilitation across feature domains serves to segregate figure from ground when the signal from a single domain is too weak to enable object detection and vanishes under conditions of stable object vision.

Contrast Sensitivity↗

PubMed1976

Physiological aspects of visual perception. II. The subcortical visual direction of behavior.

The second part of the Bennett Lecture for 1975 by Denny-Brown examined the subcortical representation of the dissociation of function described by Denny-Brown and Chambers. Complete removal in the macaque monkey of the corticomesencephalic fibers where they pass from pulvinar to colliculus, and of the colliculus, resulted in the same loss of visual object identification, binocular fixation, and visuosocial behavior that followed removal of area 17. Vision for peripheral movement and spatial orientation ("panoramic vision") remained excellent, with release of catatonia. Conversely, unilateral electrolytic lesions of the mesencephalic tegmentum produced visuospatial distortion, asymmetry of optic righting, and directional difficulties in eye movement (Parinaud syndrome and skew deviation). When bilateral, tegmental lesions produced great constriction of visual field with release of convergence and fixation spasm. Suppression of peripheral attention resulted from perceptual rivalry.

Animals↗