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Stimulus sampling and the use of distal visual cues in rats with lesions of the superior colliculus.

Rats with bilateral ablation of the superior colliculus (SC) were compared with sham-operated rats in two experiments. In the first, it was found that discrimination performance deteriorated as a function of S-R separation, to a similar extent in both groups. In this experiment, unlike earlier ones which found a deficit, the separation was introduced in a horizontal direction. In the second experiment, spatial orientation in the Morris Swimming Pool was found to be impaired in the SC rats both when the target platform was visible and when invisible. During their presence on the platform, these rats also engaged less often in upward orienting movements, although horizontal movements were of normal frequency. It is proposed (i) that there is an anisotropy in the SC's control of orienting head and eye movements in rats, and (ii) that the swimming pool deficit may be due to an impairment of ambient vision.

Animals↗

Spontaneous alternation and exploration in staggerer mutant mice.

Staggerer mutant mice were found to be less active in terms of motor activity in a maze, hole poking and rearing. Staggerer mutant mice also showed a lack of spontaneous alternation in both 2-trial and 4-trial tests. A lack of spontaneous alternation in this mutant may be due to a deficit in response inhibition or in spatial orientation, similar to that of animals with limbic lesions.

Animals↗

Impairment of auditory processing by simultaneous vestibular stimulation: psychophysical and electrophysiological data.

The aim of the experiments reported here was to demonstrate auditory-vestibular interaction both on a psychophysical and on an electrophysiological basis in humans. These results correspond to those recently obtained during simultaneous visual and vestibular stimulation and illustrate experimentally the importance of auditory information processing in spatial orientation. Time to detect the motion of a sound source is significantly increased when simultaneous vestibular stimulation is induced by passive sinusoidal head oscillations. This effect increased with the peak acceleration of the vestibular stimulus (197, 790 and 1777 degrees/s2). Vestibular influence on general auditory information processing without the quality of (object-) motion could be electrophysiologically demonstrated by means of brainstem auditory evoked potentials. The amplitude of component V generated by the inferior colliculi or by neuronal structures located slightly lower in the auditory tract was significantly reduced during concurrent vestibular stimulation. This neuronal brainstem area is a predominant location of biconvergent vestibulo-auditory neurons mediating intersensory information processing at an early neuronal level.

Adolescent↗

A primate model of Alzheimer's disease.

Animal models of Alzheimer's Disease (AD) are designed to duplicate a subset of selected neuropathological, biochemical and behavioral changes that are associated with AD. One well-studied model is based upon the assumption that the destruction of basal forebrain cholinergic neurons by injection of a neurotoxin, such as ibotenic acid, is sufficient to reproduce the cognitive impairments associated with AD. Monkeys have been trained and tested in a variety of behavioral tasks that are selective for learning and memory deficits. Typically, performance was only slightly impaired, and usually recovered to control levels with continued testing. Monkeys with basal forebrain lesions were sensitive to cholinergic antagonists but did not show a consistent benefit from treatment with cholinergic agonists. Furthermore, the memory deficits did not correlate with the degree of cholinergic cell loss. Electrophysiological studies suggest that cholinergic basal forebrain cells may help to evaluate afferent sensory stimuli for degree of novelty or familiarity, or the association of the stimuli with a subsequent reward. Consistent with these findings, monkeys with basal forebrain lesions were significantly impaired in an attention task that tested spatial orienting ability. These recent studies suggest that monkeys with basal forebrain lesions may be useful as models of the attentional deficits associated with AD.

Acetylcholine↗

Long-term impoverished housing effects on Morris maze performance after a fimbria lesion.

Male Wistar rats received bilateral Fimbria lesions and were postoperatively housed in either standard social conditions or in impoverished conditions (one rat per cage) for 2 weeks in experiment I, and for 7 months in experiment II. The effects of lesion and housing conditions were investigated in the Morris maze spatial orientation task. Fimbria lesions increased the latency to reach the platform during acquisition in both experiments, which indicates that functional recovery of the Morris maze impairment does not occur in 7 months time. Post-operative impoverishment for 2 weeks or for 7 months reduced the lesion induced deficit in Morris maze acquisition, while it had a more general effect in the trial without platform. Interestingly, the impoverishment effects were not more severe after 7 months, but even less easily detected. These findings are interpreted as if impoverishment effects the reactiveness of animals to external stimuli, which may help the animal to compensate for the lesion-induced-deficit in Morris maze learning.

Animals↗

Novel CCK-B receptor agonists: diketopiperazine analogues derived for CCK4 bioactive conformation.

Recently, we proposed a CCK-B agonist bioactive conformation characterized by an 'S' shape of the peptidic backbone which was derived from structure-activity relationships and conformational analysis of CCK4 (Trp-Met-Asp-Phe-NH2) analogues. Using this template, we report here the synthesis of cyclic CCK4 analogues which contain, in place of the Trp-Met dipeptide, a diketopiperazine moiety resulting from a cyclization between Nle and N-substituted (D)Trp residues and coupled with a small linker to Asp-Phe-NH2. Some of these compounds displayed good affinities and selectivities for the CCK-B receptor. The results are discussed in terms of size, hydrophobicity and spatial orientation of the side-chains on the diketopiperazine ring. The most potent ligand exhibited potent and full CCK-B receptor agonist properties in promoting the hydrolysis of inositol phosphates (EC50 = 8 nM) in CHO cells, stably transfected with the rat brain CCK-B receptor. This compound was also shown to be a potent selective CCK-B/gastrin receptor agonist since, it increased gastric acid secretion measured in anesthetized rats on i.v. administration. These compounds provide a rigid template for the design of non-peptide CCK-B agonists, by modification of the remaining peptide moiety.

Animals↗

Comparison of the D-lactate stereospecific dehydrogenase of Limulus polyphemus with active-site regions of L-lactate dehydrogenases.

Lactate dehydrogenase (D-lactate:NAD+ oxidoreductase, EC 1.1.1.28) from the horseshoe crab, Limulus polyphemus, a dimeric enzyme stereospecific for D-lactate, has been purified by affinity chromatography. Maleyl tryptic peptides containing arginine residues isolated from the Limulus enzyme have been characterized and sequenced. The small peptides obtained from similarly treated L-lactate-specific enzyme homologs define major portions of the substrate and coenzyme binding regions and are virtually identical among L-lactate-specific enzymes. Although the six small peptides and free arginine isolated from the Limulus enzyme indicate that the small number of arginine tryptic peptides are located in a few discrete consecutive clusters similarly to the L-lactate dehydrogenases, the peptides nevertheless show no obvious sequence homology to the corresponding peptides from L-lactate dehydrogenases. These results indicate that this lactate dehydrogenase of altered substrate specificity either evolved with major rearrangements of the active site if it evolved from an L-lactate dehydrogenase, or that D-lactate dehydrogenases have evolved from a different protein. The results contradict proposed models which suggest that minor changes in the spatial orientation of pyruvate resulting from minimal rearrangement of the active site could accommodate the change in substrate specificity.

Amino Acid Sequence↗

Site-directed mutagenesis of the cGMP phosphodiesterase gamma subunit from bovine rod outer segments: role of separate amino acid residues in the interaction with catalytic subunits and transducin alpha subunit.

The recombinant and 21 mutant phosphodiesterase (PDE) gamma subunit (PDE gamma) genes were expressed by sequential transcription and translation in vitro. Inhibitory properties of these mutants and their interactions with PDE catalytic and transducin alpha subunits were studied. The interaction of the PDE gamma subunit with the catalytic ones proceeds in two steps--primary binding and inhibition. The central region of the PDE gamma molecule enriched with the basic amino acid residues (particularly, Lys-29, Lys-31 and Arg-33), is involved in the primary binding, and the PDE gamma C-terminus plays the key role in inhibition. The spatial orientation of the C-terminus is of great importance here. The PDE gamma C-terminus also affects binding to catalytic moieties.

3',5'-Cyclic-GMP Phosphodiesterases↗

Lateral eye movements as an indication of hemispheric preference: an EEG validation study.

The hemispheric asymmetry model of lateral eye movements (LEM), hypothesizing a relation between a predominance of lateral gazes to one side with a predominance of activity in the hemisphere contralateral to the preferred direction of gaze, was tested in male, right-handed subjects. During presentation of cognitive tasks (verbal synonym tasks and spatial orienting tasks) the decrease in alpha-power from a reference period to each of four activation periods (anticipation, task-presentation, first LEM, answer) for 6 derivations from each hemisphere was calculated using the method of 'Event-related desynchronisation'. Evidence for the hypothesis was found only during the EEG-epoch one second before the answer. Discrimination between subjects with a predominance of left vs right eye movements (left- vs right-movers) was best at temporal (T3, T4) and central (C3, C4) sites. These results were significant for the entire alpha-band (8-12 Hz) and--even more pronounced--for the alpha-2-band (10-12 Hz). The alpha-1-band (8-10 Hz) did not produce significant differences. Comparing the two types of tasks, synonym tasks yielded results which were more congruent with the hypothesis. The results suggest that lateral eye movements indicate individual differences in hemispheric EEG-asymmetries under certain experimental conditions (task, segment of EEG-analysis, site, frequency band).

Adult↗

Acceleration-sensitivity threshold of Physarum.

Free-living cells show distinct gravisensitivities and often use the gravity ('g') vector for their spatial orientation. The rhythmic contractions of the ameboid Myxomycete (acellular slime mold) Physarum polycephalum are a sensitive parameter which can be modified by external stimuli. Space experiments and ground-based 0 x g simulation studies established that the contraction period transiently decreases after a transition from 1 x g to 0 x g with a back-regulating process starting after 30 min. For determination of the threshold of acceleration sensitivity, a slow-rotating centrifuge microscope (NIZEMI--Niedergeschwindigkeits-Zentrifugenmikroskop) was used, providing in space accelerations from 0 x g to 1.5 x g. A stepwise acceleration increase revealed that the lowest acceleration level capable of inducing a response was 0.1 x g. The response to the acceleration increase was an increase in contraction period, in contrast to a stimulus deprivation, which led to a period decrease. The time schedule of the acceleration responses and back-regulating process seems to be fixed, suggesting that every acceleration being above the threshold can induce a complete response-regulation process. The low acceleration-sensitivity threshold favors rather large and dense cell organelles as candidates for the gravity receptor in Physarum.

Acceleration↗

Three-dimensional human somatosensory evoked potentials.

Median nerve somatosensory evoked potentials were recorded from 30 normal adults using conventional scalp derivations and an orthogonal bipolar surface electrode montage. This allowed the determination of the spatial orientation of the hypothetical centrally located equivalent dipole derived from the evoked response recorded in 3-dimensional voltage space. The 3-dimensional voltage trajectory describing changes in equivalent dipole orientation and magnitude revealed 4 major apices between 5 and 25 msec, 3 of which corresponded to the traditional P14, N20 and P25 peaks. A fourth apex at 17 msec was not as evident in the conventional recordings and signaled a transition from a vertical P14-N18 generator process to a horizontal N20 generator process. The normal within- and between-subject variability of trajectory apices, segments and planes are described, along with the theoretical and practical implications of this recording technique.

Adult↗

Le Fort I maxillary osteotomy: is it possible to accurately produce planned pre-operative movements?

The planned preoperative maxillary movements for five groups of patients requiring orthognathic surgery were prospectively compared to the actual surgical movements achieved in the operating theatre. There was a very poor success rate in achieving predicted movements in all the patient groups. There is a need to test and implement a reliable method of assisting the surgeon in spatially orientating the jaws on the operating table.

Cephalometry↗

Gravity as an obligatory factor in normal higher plant growth and development.

Gravity may influence different aspects of plant activity. The present report deals with two questions: gravity as an ecological factor determining spatial orientation of plant growth; and second, a possible requirement for gravity in the process of normal growth, morphogenesis and generative development of plants.

Arabidopsis↗

Survey of the vestibulum, and behavior of Xenopus laevis larvae developed during a 7-days space flight.

Aquatic animals have almost no body weight related proprioception for spatial orientation. Xenopus larvae, like fish, maintain their attitude in water by continuous correction with their fin(s). For these reasons a special performance of the equilibrium system compared to terrestrial animals is necessary. Evidently fish therefore have more compact (dense) otoliths; Xenopus larvae have less dense otolith (membranes) similar to land vertebrates; but their sacculus-otoliths are vertically positioned, which also may lead to a higher g-sensitivity. For plausibility reasons gravity should influence the embryonic development of gravity receptors. Yet, evaluations of photographs taken from the surface of cut deep-frozen objects by incident light show no aberration of the shape of the whole vestibulum and of the shape, density, size and position of the otolith membrane in larvae developed under near-zero g (NEXPA-BW-STATEX in D-1-Mission). The further evaluation of the "weightless-larvae" revealed a probably not yet described statolith-like formation in the dorsal wall of the vestibulum. In the weightless larvae this formation outnumbers, also qualitatively, strongly the l-g controls. An extra result is the lack of striking effects of cosmic radiation on the embryonic development of the flown Xenopus eggs. The swimming behavior of the larvae which was observed about one hour after landing of the Space Shuttle showed a typical anomaly (loop swimming), which is known from larvae developed on the clinostat or from fish flown aboard Apollo capsules.

Animals↗

Effects of rectilinear acceleration, caloric and optokinetic stimulation of human subjects in the Spacelab D-1 mission.

A set of vestibular experiments was performed during the course of the German Spacelab D-1 mission from 30 October to 6 November 1985 by a consortium of experimenters from various european countries. Similar to the Spacelab SL-1 mission all of the scientific crew members were theoretically and practically trained for the experiments. Baseline measurements for all tests were collected 113, 86, 44, 30 and 18 days prior to the mission and compared with data taken inflight, on the landing day and the consecutive 7 to 14 days. The hardware comprised mainly a motordriven accelerating platform, the SPACE SLED, and the vestibular helmet, a multi-purpose instrument in support of a variety of vestibular experiments including air-calorisation of the ears, optokinetic stimulation pattern presentation and optical and nystagmographic recording of eye movements. Measurements of the threshold for the perception of detection of whole body movement did not reveal any dramatic changes in the 2 measured axes inflight when compared to preflight values. Early postflight values show a significantly elevated threshold for all axes in 3 out of 4 subjects. The caloric nystagmus, already found during the SL-1 mission, was confirmed on all three tested subjects during the D-1 mission. It's amplitude and in some instances it's direction were influenced by horizontal acceleration on the SLED. The amplitude of optokinetic nystagmus increased when subjects were allowed to free-float over that seen when subjects were fixed. Stimulation of the neck receptors by roll movements of the body against the fixated head resulted in illusory object motion to the contralateral side. Torsional movements of the eyes during such neck receptor stimulation was present inflight and postflight, while it had not been observed preflight. Most results point to a reduction of otolithic effects in favour of visual and proprioceptive influences for spatial orientation.

Acceleration↗

Structure of cress root statocytes in microgravity (Bion-10 mission).

Experiments on primary roots of Lepidium sativum L. have been performed on board the Bion-10 satellite. The experimental set-up was extremely miniaturized and completely automatic. The results demonstrate the effectiveness of the instrumentation. The spatial orientation, growth, root cap differentiation and statocyte structure of roots grown under microgravity (MG) have been compared with control roots grown on the ground (GC) and in a 1G-reference centrifuge in space (RC). Root length and cap shape did not differ between MG and control samples. Under MG, the mean distance of the statoliths from the distal cell wall of the statocytes increased significantly, the mean distance of the mitochondria decreased and the nucleus did not change its position in comparison to both controls. The number and the shape of the amyloplasts (statoliths) were not influenced by the space flight factors, but their size as well as their relative area in the cell decreased. The number of starch grains per statolith as well as their size and shape changed under MG. In MG and RC samples the number of lipid bodies in the statocytes was higher and the relative area larger than in GC samples. The relative area occupied by vacuoles was greater in RC statocytes than in GC and MG statocytes. These results partly confirm and, in addition, extend the data from earlier experiments in space.

Microscopy, Electron↗

Functional aspects of ribosomal proteins.

A short personal recollection of HG Wittmann is given with emphasis on his basic contribution to the structure of the ribosome, in particular the ribosomal proteins. With these considerations in mind, two interrelated problems are reviewed here. The first relates to the internal symmetry both in tRNA and in the tetrameric L12-protein complex. The second problem to be addressed relates to the dynamics of transfer RNA in the ribosome and the role of L12 proteins in this process. The importance of electrostatic repulsion in the maintenance of the mutual spatial orientation of tRNAs and L12 in the ribosome is emphasized in relation to a pendulum model for how L12 may steer translocation.

Amino Acid Sequence↗

Capacitance in ant cuticle is frequency dependent: a statistical model.

The capacitance and the electric resistance of the cuticle of the ant Cataglyphis bicolor nigra Andr é (Hymenoptera, Formicinae ) were measured. The measurements were done at the frequencies 100 Hz and 1000 Hz and at a temperature range of 27.5-45 degrees C. Inverse correlation was observed between the capacitance and the frequency, so that at the higher frequency the capacitance was lower. Thus, in some instances, at 1000 Hz the capacitance ranged between 0.49 and 2. 16nF , while at 100 Hz it ranged between 5.74 and 19. 39nF at the measured temperature range. A similar inverse correlation was detected also between the resistance and the frequency. At 1000 Hz, the resistance values in some specimens ranged between 0.166 and 0.278 M omega whereas at 100 Hz they varied between 0.342 and 0.883 M omega. At both frequencies measured there was a temperature-dependence of the capacitance and of the electric resistance. With increase in temperature there was increase in the capacitance and a decrease in the resistance. Invariably, the trend of cuticular behavior was similar under cooling as under warming, but the values differed, creating a gap (hysteresis). Under cooling the resistance values were higher and the reverse was true for the capacitance. A statistical model is offered which graphically describes the behavior of the ant cuticle (resistance and capacitance) under changes in temperature and frequency. X-ray analysis of the cuticle revealed the presence of Ca as the most prominent element. Additional elements, but less prominent were P, S and K. It also contains Fe and Zn. The finding of a correlation between the capacitance and the frequency might lead to the following conclusions: that the measured system contains polarized substances; that the measured value in each case represents a resultant of values obtained from the measurement of more than one electrical circle (and probably more than one network of electrical circles); and that possibly a combination of (a) and (b) prevails. Presumably these changes in the capacitance and resistance at different temperatures and frequencies indicate that the ant cuticle is capable of responding to changes in the physical ambience , thus promoting proper ant spatial orientation and the pursuant behavior.

Animals↗