Horizontal vestibuloocular reflex evoked by high-acceleration rotations in the squirrel monkey. II. Responses after canal plugging.
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The horizontal angular vestibuloocular reflex (VOR) evoked by high-frequency, high-acceleration rotations was studied in four squirrel monkeys after unilateral plugging of the three semicircular canals. During the period (1-4 days) that animals were kept in darkness after plugging, the gain during steps of acceleration (3, 000 degrees /s(2), peak velocity = 150 degrees /s) was 0.61 +/- 0.14 (mean +/- SD) for contralesional rotations and 0.33 +/- 0.03 for ipsilesional rotations. Within 18-24 h after animals were returned to light, the VOR gain for contralesional rotations increased to 0. 88 +/- 0.05, whereas there was only a slight increase in the gain for ipsilesional rotations to 0.37 +/- 0.07. A symmetrical increase in the gain measured at the plateau of head velocity was noted after animals were returned to light. The latency of the VOR was 8.2 +/- 0. 4 ms for ipsilesional and 7.1 +/- 0.3 ms for contralesional rotations. The VOR evoked by sinusoidal rotations of 0.5-15 Hz, +/-20 degrees /s had no significant half-cycle asymmetries. The recovery of gain for these responses after plugging was greater at lower than at higher frequencies. Responses to rotations at higher velocities for frequencies >/=4 Hz showed an increase in contralesional half-cycle gain, whereas ipsilesional half-cycle gain was unchanged. A residual response that appeared to be canal and not otolith mediated was noted after plugging of all six semicircular canals. This response increased with frequency to reach a gain of 0.23 +/- 0.03 at 15 Hz, resembling that predicted based on a reduction of the dominant time constant of the canal to 32 ms after plugging. A model incorporating linear and nonlinear pathways was used to simulate the data. The coefficients of this model were determined from data in animals with intact vestibular function. Selective increases in the gain for the linear and nonlinear pathways predicted the changes in recovery observed after canal plugging. An increase in gain of the linear pathway accounted for the recovery in VOR gain for both responses at the velocity plateau of the steps of acceleration and for the sinusoidal rotations at lower peak velocities. The increase in gain for contralesional responses to steps of acceleration and sinusoidal rotations at higher frequencies and velocities was due to an increase in the gain of the nonlinear pathway. This pathway was driven into inhibitory cutoff at low velocities and therefore made no contribution for rotations toward the ipsilesional side. (+info)
Behavioral effects of cocaine: interactions with D1 dopaminergic antagonists and agonists in mice and squirrel monkeys.
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The present study compared interactions among dopamine D1-like agonists and partial agonists with cocaine on the locomotor stimulant effects of cocaine, as well as the discriminative-stimulus effects of cocaine, and effects of cocaine on rates of responding. Cocaine alone produced a dose-related stimulation of locomotor activity in Swiss-Webster mice and a dose-related increase in the proportion of responses on the cocaine-appropriate response key in squirrel monkeys (Saimiri sciureus) trained to discriminate cocaine (0.3 mg/kg i.m.) from saline. None of the D1 dopaminergic agents fully reproduced these effects, with SKF 77434 producing marginal stimulation of locomotor activity and SCH 23390, SCH 39166, and SKF 77434 producing some, although incomplete substitution for cocaine in monkeys discriminating cocaine. The D1 dopamine antagonists SCH 23390, SCH 39166, and A-69024 dose-dependently shifted the cocaine dose-effect curve for locomotor activity to the right and decreased the efficacy of cocaine. The same compounds shifted the discriminative-stimulus effects of cocaine to the right without altering efficacy of cocaine. In contrast to the effects on locomotor activity, the maximal shift to the right in the discriminative-stimulus effects of cocaine was approximately 3-fold, with higher doses of the antagonists producing no greater shifts in the cocaine dose-effect curve than with intermediate doses. The partial D1 agonists (+/-)-SKF 38393, (+)-SKF 38393, and SKF 77434 also dose-dependently shifted the dose-effect curve for locomotor stimulant effects to the right and decreased the maximal effect of cocaine. These compounds only shifted the discriminative-stimulus effects of cocaine to a 2-fold maximum. In general, cocaine effects on rates of responding in the subjects discriminating cocaine from saline were only minimally antagonized by coadministration of the D1 dopaminergic agents. Both potency for producing behavioral effects alone and in antagonizing the effects of cocaine were related to binding affinities assessed by displacement of [(3)H]SCH 23390 from rat striatum. These results suggest that actions mediated by D1-like receptors contribute to the behavioral effects of cocaine. However, the various limitations to the degree of antagonism accomplished indicate that D1-like dopaminergic actions appear to be more involved in the effects of cocaine on locomotor activity, relatively less involved in the discriminative-stimulus effects of cocaine, and least involved in the effects of cocaine on operant response rates. This differential involvement of D1 dopamine receptors in these various behavioral effects of cocaine suggests problems in predicting clinical efficacy of at least D1 receptor antagonists as potential treatments for cocaine abuse. Additional studies are necessary to determine whether the antagonism of cocaine can predict therapeutic efficacy at all, and, if so, which effects when antagonized are the best predictors. (+info)
HERV-F, a new group of human endogenous retrovirus sequences.
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Using primers from a conserved region of the XA34 human endogenous retrovirus (HERV) family, four pol fragments originating from new members of the family were amplified from human genomic DNA. Southern blot analysis demonstrated similar hybridization patterns in human, chimpanzee and orangutan and distinct hybridization to macaque DNA. The probes also exhibited weaker hybridization to squirrel monkey DNA. Using large genomic clones, two full-length XA34-related HERVs have been identified. One of the HERVs is located downstream of a human Kruppel-related zinc finger protein gene, ZNF195. Both of the newly identified long terminal repeats have potential TATA boxes, poly(A) signals and transcription factor-binding sites but they differ to a high degree, especially in the U3 region. The primer-binding sites were found to be homologous to tRNA(Phe) (TTC), and therefore these new HERVs have been given the name HERV-F. The closest relatives to the HERV-Fs are the RTVLH-RGH family. Phylogenetic analyses of the Gag, Pol and Env regions are discussed. Both of the newly identified HERV-Fs were shown to contain protease, reverse transcriptase, integrase and env regions and had characteristic deletions in the integrase and env regions. In addition, the capsid protein gene of gag and two conserved zinc-binding motifs that are characteristic of a potential nucleic acid-binding protein were also identified. Apart from an ORF spanning the protease of one HERV-F, no other longer ORFs were found. (+info)
Enantioselectivity of odor perception in squirrel monkeys and humans.
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With use of a conditioning paradigm, the ability of six squirrel monkeys to distinguish between 10 pairs of enantiomers, i.e., odorants that are identical except for chirality, was investigated. As a group, the animals were only able to discriminate between the optical isomers of alpha-pinene, carvone, limonene, and fenchone, whereas they failed to distinguish between the (+) and (-) forms of beta-citronellol, menthol, rose oxide, 2-butanol, alpha-terpineol, and camphor. With use of a triple forced-choice procedure, 10 human subjects were tested for their ability to discriminate between the same enantiomeric odor pairs in parallel and, with the exception of fenchone, showed a very similar pattern of performance compared with the squirrel monkeys. These findings support the assumption that human and nonhuman primates may share common principles of odor quality perception. Furthermore, the results suggest that, in both species, enantioselective molecular odor receptors may only exist for some, but not all volatile enantiomers and thus that chiral recognition of odorants is not a general phenomenon, but may be restricted to some substances. (+info)
The open reading frame 57 gene product of herpesvirus saimiri shuttles between the nucleus and cytoplasm and is involved in viral RNA nuclear export.
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The herpesvirus saimiri open reading frame (ORF) 57 is homologous to genes identified in all classes of herpesviruses. It has previously been shown to regulate gene expression through a posttranscriptional mechanism. We demonstrate in this report that the expression of the ORF 57 protein leads to the cytoplasmic accumulation of glycoprotein B and capsid mRNAs. We also demonstrate that ORF 57 has the ability to specifically bind viral RNA transcripts. Utilizing an interspecies heterokaryon assay, we show that ORF 57 has the ability to shuttle between the nucleus and the cytoplasm. Furthermore, we show that ORF 57 contains a relatively leucine-rich sequence which shares some homology with nuclear export signals (NES) found in a number of proteins with the ability to shuttle between the nucleus and the cytoplasm. Moreover, we demonstrate that the ORF 57 NES enables the nuclear export of a heterologous protein and that mutation of the conserved leucine residues contained within the ORF 57 NES signal abrogates the ability of the ORF 57 protein to shuttle between the nucleus and cytoplasm. These results suggest that ORF 57 is involved in mediating the nuclear export of viral transcripts. (+info)
Discriminative stimulus effects of zolpidem in squirrel monkeys: comparison with conventional benzodiazepines and sedative-hypnotics.
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The present study examined whether zolpidem, an imidazopyridine with selectivity for benzodiazepine (BZ)/gamma-aminobutyric acid(A) receptors containing the alpha1-subunit, had discriminative stimulus effects similar to typical BZs and other sedative/hypnotic drugs in primates. Squirrel monkeys (Saimiri sciureus) were trained to discriminate zolpidem (1.0 mg/kg i.v.) from vehicle under a 10-response fixed-ratio schedule of food delivery. Under test conditions, zolpidem (0.1-3.0 mg/kg) increased responding on the drug lever to an average maximum of 90% of total responding. When pretreatment times were varied from 5 to 50 min, the discriminative stimulus effects of zolpidem were maximal at 5 min and near control levels 35 min after administration. Flumazenil antagonized both the discriminative stimulus and rate-decreasing effects of zolpidem in a dose-dependent and surmountable fashion (in vivo apparent pA(2) values of 7.3 and 6.6 for the discriminative stimulus and rate-suppressing effects, respectively). The BZs triazolam, midazolam, diazepam, and N-desmethyldiazepam engendered dose-related increases in drug-lever responding that reached zolpidem-like levels (90%) in the majority of monkeys tested. In contrast, lorazepam, chlordiazepoxide, and oxazepam engendered average maximums of 70% or less and substituted fully for zolpidem in one or two monkeys only. Representative barbiturates as well as drugs that bind to non-BZ sites (muscimol, baclofen, buspirone, cyproheptadine, diphenhydramine) engendered 0 to 45% of responses on the drug lever up to doses that markedly reduced response rate. These results support the view that zolpidem's selectivity for the alpha1-subunit of the BZ/gamma-aminobutyric acid(A) receptor complex confers a distinctive profile of interoceptive effects that overlaps partially with those of typical BZs but not with those of barbiturates. (+info)
Centromere repositioning.
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Primate pericentromeric regions recently have been shown to exhibit extraordinary evolutionary plasticity. In this paper we report an additional peculiar feature of these regions that we discovered while analyzing, by FISH, the evolutionary conservation of primate phylogenetic chromosome IX. If the position of the centromere is not taken into account, a relatively small number of rearrangements must be invoked to account for interspecific differences. Conversely, if the centromere is included, a paradox emerges: The position of the centromere seems to have undergone, in some species, an evolutionary history independent from the surrounding markers. A significant number of additional rearrangements must be proposed to reconcile the order of the markers with centromere position. Alternatively, the evolutionary emergence of neocentromeres can be postulated. (+info)
Factors influencing the frequency of fluorescence transients as markers of peri-infarct depolarizations in focal cerebral ischemia.
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BACKGROUND AND PURPOSE: Peri-infarct depolarizations (PIDs) that occur in ischemic boundary zones of the cerebral cortex of experimental animals have been shown to promote rather than simply to indicate the evolution of the lesion and are especially prominent in the rat. To study the influence of one factor, species, on PID incidence, we compared the frequency of PIDs in a primate species, the squirrel monkey, with that in the cat after middle cerebral artery occlusion. Plasma glucose was reviewed as a possible cause of interexperiment variability in the cat experiments. METHODS: In open-skull experiments under chloralose anesthesia, changes in cortical fluorescence believed to indicate NADH/NAD(+) redox state, as markers of PIDs, were recorded by serial imaging of the cortical surface in vivo for 4 hours after middle cerebral artery occlusion. RESULTS: Fluorescence transients occurred in squirrel monkeys at a frequency (mean+/-SD) of 0.7+/-0.8 hours(-1) (n=5), which was not significantly less than in that observed in cats (1.3+/-1.6 hours(-1), n=8). Data from the cat experiments indicated a relationship between number of transients (dependent) and plasma glucose, with a striking increase in PID frequency in association with values of mean postocclusion plasma glucose <4.1 mmol/L (Mann-Whitney U=15.0, P=0.034); this observation agrees well with other published findings. CONCLUSIONS: Transient changes in fluorescence strongly suggestive of peri-infarct depolarizations, either transient or terminal, occur and propagate in the ischemic cerebral cortex of a nonhuman primate. The results also suggest that the relationship of frequency of peri-infarct depolarizations with plasma glucose requires further examination, to confirm the finding and to determine a safe lower limit for a target range for control of plasma glucose if insulin is used in the management of patients with cerebral ischemia. (+info)