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C D Barnes

Publications and source records attributed to C D Barnes.

At least 37 records · Page 2Linked to original sources

Pontospinal transmitters and their distribution.

The dorsolateral pontine tegmentum of the cat is known to contain a large population of catecholaminergic neurons. Additionally, several studies have also shown the presence of other neurochemicals (acetylcholine, enkephalin, neuropeptide Y, serotonin, somatostatin and substance P). In this study, we have employed retrograde transport of horseradish peroxidase in combination with immunocytochemistry to determine the locations of pontospinal neurons which contain catecholamine, enkephalin, neuropeptide Y, and serotonin. Furthermore, we have combined the retrograde transport of Fast Blue and immunofluorescence histochemistry to determine whether enkephalin-containing neurons are catecholaminergic. All pontospinal neurons, irrespective of the neurochemical content, were observed in the ventral and lateral parts of the dorsolateral pontine tegmentum at coronal levels P1.8-P4.0. These neurons were located in the nuclei locus coeruleus alpha and subcoeruleus and the Kölliker-Fuse nucleus. A high concentration of these neurons was evident in the Kölliker-Fuse nucleus when compared to the nuclei locus coeruleus alpha and subcoeruleus. Quantitative data have revealed that enkephalin is contained in a large proportion of the pontospinal catecholaminergic neurons (75%). The observations suggest that catecholaminergic neurons may contain one or more putative peptide neurotransmitters.

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Norepinephrine effects on spinal motoneurons.

Intracellular recordings from cat spinal motoneurons in situ demonstrated that microiontophoretic application of NE with low-intensity ejection currents produces a slowly developing, small-amplitude depolarization of the cells, in contrast to early reports of NE-induced hyperpolarization. This depolarization was associated with an increase in excitability of the cells and a decrease in membrane conductance. These observations are consistent with the hypothesis that NE reduces potassium conductance in spinal motoneurons as has been proposed for facial motoneurons (VanderMaelen and Aghajanian, 1980) and thalamic neurons (McCormick and Prince, 1988). The time course of the facilitatory effects of NE on cat motoneuron excitability recorded intracellularly agreed very closely with the time course of NE-induced facilitation of glutamate-evoked excitability in rat spinal motoneurons recorded extracellularly. The similarity of the observations in rats and cats suggests that NE functions generally to enhance mammalian motoneuron responsiveness to excitatory input.

Action Potentials↗

Locus coeruleus control of spinal motor output.

Using electrophysiological techniques, we investigated the functional properties of the coeruleospinal system for regulating the somatomotor outflow at lumbar cord levels. Many of the fast-conducting, antidromically activated coeruleospinal units were shown to exhibit the alpha 2-receptor response common to noradrenergic locus coeruleus (LC) neurons. Electrically activating the coeruleospinal system potentiated the lumbar monosynaptic reflex and depolarized hindlimb flexor and extensor motoneurons via an alpha 1-receptor mechanism. The latter synaptically induced membrane depolarization was mimicked by norepinephrine applied iontophoretically to motoneurons. That LC inhibited Renshaw cell activity and induced a positive dorsal root potential at the lumbar cord also reinforced LC's action on motor excitation. We conclude that LC augments the somatomotor output, at least in part, via an alpha 1-adrenoceptor-mediated excitation of ventral horn motoneurons. Such process is being strengthened by LC's suppression of the recurrent inhibition pathway as well as by its presynaptic facilitation of afferent impulse transmission at the spinal cord level.

Action Potentials↗

Responses of locus coeruleus neurons to labyrinth and neck stimulation.

The electrical activity of a large population of locus coeruleus (LC)-complex neurons, some of which were antidromically activated by stimulation of the spinal cord at T12-L1, was recorded in precollicular decerebrate cats during labyrinth and neck stimulation. Some of these neurons showed physiological characteristics attributed to norepinephrine (NE)-containing LC neurons, i.e., (i) a slow and regular resting discharge; (ii) a typical biphasic response to compression of the paws consisting of short impulse bursts followed by a silent period, which was attributed to recurrent and/or lateral inhibition of the corresponding neurons; and (iii) a suppression of the resting discharge during episodes of postural atonia, associated with rapid eye movements (REM), induced by systemic injection of an anticholinesterase, a finding which closely resembled that occurring in intact animals during desynchronized sleep. Among the neurons tested, 80 of 141 (i.e., 56.7%) responded to the labyrinth input elicited by sinusoidal tilt about the longitudinal axis of the whole animal at the standard parameters of 0.15 Hz, +/- 10 degrees, and 73 of 99 (i.e., 73.7%) responded to the neck input elicited by rotation of the body about the longitudinal axis at the same parameters, while maintaining the head stationary. A periodic modulation of firing rate of the units was observed during the sinusoidal stimuli. In particular, most of the LC-complex units were maximally excited during side-up tilt of the animal and side-down neck rotation, the response peak occurring with an average phase lead of about +17.9 degrees and +34.2 degrees with respect to the extreme animal and neck displacements, respectively. Similar results were also obtained from the antidromically identified coeruleospinal (CS) neurons. The degree of convergence and the modalities of interaction of vestibular and neck inputs on LC-complex neurons were also investigated. In addition to the results described above, the LC-complex neurons were also tested to changing parameters of stimulation. In particular, both static and dynamic components of single unit responses were elicited by increasing frequencies of animal tilt and neck rotation. Moreover, the relative stability of the phase angle of the responses evaluated with respect to the animal position in most of the units tested at increasing frequencies of tilt allowed the conclusion to attribute these responses to the properties of macular ultricular receptors. This conclusion is supported by the results of experiments showing that LC-complex neurons displayed steady changes in their discharge rate during static tilt of the animal.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Tonic enhancement of the sensitivity of baroreceptor reflex response by endogenous substance P in the rat.

Modulation of baroreceptor reflex (BRR) by endogenous substance P (SP) in the brain was investigated in rats anesthetized with pentobarbital sodium. Intracerebroventricular administration of the undecapeptide (15 or 30 nmol) and its antagonist, (D-Pro2, D-Trp7,9)-SP (30 or 60 nmol) or SP antiserum (1:20), respectively, promoted a significant increase and decrease in the sensitivity of BRR response. Prolonging the endogenous activity of SP with the aminopeptidase blocker, bestatin (200 nmol) or with the endopeptidase-24.11 inhibitor, phosphoramidon (200 nmol) significantly augmented the same reflex. Combining the undecapeptide with either peptidase blocker, moreover, promoted additional potentiation of the BRR response. On the other hand, simultaneous administration of bestatin and (D-Pro2, D-Trp7,9)-SP produced a reduction of the augmented effect of bestatin on the sensitivity of BRR response. Bilateral microinjection of SP (600 pmol) or an antiserum against SP (1:20) into the nucleus tractus solitarius (NTS) elicited respectively an enhancement of and reduction in the BRR response. These data suggest that neurons that contain SP may participate in central cardiovascular control by tonically enhancing the sensitivity of the BRR response, possibly via an action on the NTS.

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Tonic suppression of baroreceptor reflex by endogenous neurotensin in the rat.

We evaluated the modulatory role of endogenous neurotensin (NT) in baroreceptor reflex (BRR) response in Sprague-Dawley rats anesthetized with pentobarbital sodium. Intracerebroventricular (i.c.v.) administration of NT (15 or 30 nmol) significantly reduced the sensitivity of the BRR response. Blocking the endogenous activity of the tridecapeptide with its specific antagonist, (D-Trp11)-NT (4 or 8 nmol) or antiserum against NT (1:20); or inhibiting the aminopeptidases with bestatin (200 nmol), on the other hand, promoted a potentiation of BRR response. When administered together with bestatin (200 nmol), the suppressive effect of NT (15 nmol) on the BRR response was further enhanced, as was the augmentative action of (D-Trp11)-NT (4 nmol). Upon microinjection into the bilateral nucleus tractus solitarius (NTS), NT (600 pmol) and (D-Trp11)-NT (150 pmol) respectively elicited a reduction and enhancement of the BRR response. These results suggest that neurons that contain NT may participate in central cardiovascular regulation by tonically suppressing the BRR, possibly via an action on the NTS where baroreceptor afferents terminate.

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Localization of enkephalinergic neurons in the dorsolateral pontine tegmentum projecting to the spinal cord of the cat.

The dorsolateral pontine tegmentum of the cat is known to contain enkephalinergic neurons, with most of the enkephalin co-contained in the catecholaminergic neurons; however, enkephalinergic cells projecting to the spinal cord have not been identified. This study employs retrograde transport of horseradish peroxidase in combination with methionine-enkephalin or tyrosine hydroxylase immunocytochemistry to 1) determine the locations of pontospinal enkephalinergic neurons and 2) compare these with the locations of pontospinal catecholaminergic neurons. Pontospinal enkephalinergic neurons were observed in the nuclei locus coeruleus and subcoeruleus and the Kölliker-Fuse nucleus. A high concentration of these neurons was evident in the Kölliker-Fuse nucleus when compared to the nuclei locus coeruleus and subcoeruleus (P less than .01). Both the enkephalinergic and catecholaminergic neurons projecting to the spinal cord were located in the same general areas of the dorsolateral pontine tegmentum and there was no significant difference in the mean diameters of these two neuronal types (P greater than .05). Quantitative data concerning the pontospinal enkephalinergic neurons correlated well with previous data on pontospinal catecholaminergic neurons (Reddy et al., Brain Res. 491:144-149, '89). A majority of the descending neurons from the dorsolateral pontine tegmentum contain enkephalin (72-80%) and catecholamine (80-87%). The observations suggest that enkephalin is contained in many of the pontospinal catecholaminergic neurons.

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Responses of locus coeruleus and subcoeruleus neurons to sinusoidal stimulation of labyrinth receptors.

In precollicular decerebrate cats the electrical activity of 141 individual neurons located in the locus coeruleus-complex, i.e. in the dorsal (n = 41) and ventral parts (n = 67) as well as in the locus subcoeruleus (n = 33), was recorded during sinusoidal tilt about the longitudinal axis of the whole animal, leading to stimulation of labyrinth receptors. Some of these neurons showed physiological characteristics attributed to the norepinephrine-containing locus coeruleus neurons, namely, (i) a slow and regular resting discharge, and (ii) a typical biphasic response to fore- and hindpaw compression consisting of short impulse bursts followed by a silent period, which has been attributed to recurrent and/or lateral inhibition of the norepinephrine-containing neurons. Furthermore, 16 out of the 141 neurons were activated antidromically by stimulation of the spinal cord at T12 and L1, thus being considered coeruleospinal or subcoeruleospinal neurons. A large number of tested neurons (80 out of 141, i.e. 56.7%) responded to animal rotation at the standard frequency of 0.15 Hz and at the peak amplitude of 10 degrees. However, the proportion of responsive neurons was higher in the locus subcoeruleus (72.7%) and the dorsal locus coeruleus (61.0%) than in the ventral locus coeruleus (46.3%). A periodic modulation of firing rate of the units was observed during the sinusoidal stimulus. In particular, 45 out of the 80 units (i.e. 56.2%) were excited during side-up and depressed during side-down tilt (beta-responses), whereas 20 of 80 units (i.e. 25.0%) showed the opposite behavior (alpha-responses). In both instances, the response peak occurred with an average phase lead of about + 18 degrees, with respect to the extreme side-up or side-down position of the animal; however, the response gain (imp./s per deg) was, on average, more than two-fold higher in the former than in the latter group. The remaining 15 units (i.e. 18.7%) showed a prominent phase shift of this response peak with respect to animal position. Similar results were obtained from the subpopulation of locus coeruleus-complex neurons which fired at a low rate (less than 5.0 imp./s), as well as for the antidromically identified coeruleospinal neurons. The response gain of locus coeruleus-complex neurons, including the coeruleospinal neurons, did not change when the peak amplitude of tilt was increased from 5 degrees to 20 degrees at the fixed frequency of 0.15 Hz. This indicates that the system was relatively linear with respect to the amplitude of displacement.(ABSTRACT TRUNCATED AT 400 WORDS)

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Evaluation of neuron-based sensing with the neurotransmitter serotonin.

Results are presented on the development of a novel biosensor which will use neurons or neuronal components as both the recognition elements and primary transducers for analyte quantitation. This concept is demonstrated and evaluated by exposing identified neurons from the visceral ganglia of the pond snail Limnea stagnalis to the model analyte serotonin. Experiments reveal a reversible, concentration-dependent increase in the rate of spontaneous action potential generation, over a concentration range of four orders of magnitude. Studies with the antagonist methysergide verify that this response is mediated through serotonin-sensitive receptors. Exposure of the neurons to serotonin causes the firing frequency to rapidly increase to a maximum and then slowly diminish to a sub-optimal level. It was found that the maximum frequency provides an indication of chemical concentration that is repeatable. Data are also presented which further advance the field of neuronal biosensing by demonstrating both the effects of cell to cell variability on response reproducibility and the effects of the desensitizing response on the operation of a neuron-based sensor in both a continuous and discontinuous mode.

Action Potentials↗

Raphé-produced excitation of spinal cord motoneurons in the cat.

In all motoneurons examined, both flexor and extensor, raphé (pallidus) stimulation consistently produced an excitatory postsynaptic potential (EPSP). Upon interaction with a group Ia EPSP there was summation resulting in neuronal discharge. The raphé-induced EPSP also facilitated the initial segment-somadendritic coupling and hence the motoneuron excitability. These data support an excitatory role for raphé-spinal fibers on cat hindlimb motoneurons.

Action Potentials↗

Spinally projecting noradrenergic neurons of the dorsolateral pontine tegmentum: a combined immunocytochemical and retrograde labeling study.

Two to three days following injection of horseradish peroxidase (HRP) into the spinal cords of 5 cats, the animals were sacrificed and perfused, and the brainstems removed and sectioned. The sections were then processed for HRP and, immunocytochemically, for tyrosine hydroxylase (TH). The dorsolateral pontine tegmentum was divided into the locus coeruleus, subcoeruleus and Kölliker-Fuse nucleus; the mean percentage of pontospinal neurons containing TH were found to be 85.5 +/- 2.5 (S.E.M.), 79.6 +/- 5.6 and 87.1 +/- 3.1, respectively. The cell diameters of locus coeruleus cells were also measured.

Adrenergic Fibers↗

The actions of two monoamines on spinal motoneurons from stimulation of the locus coeruleus in the cat.

The present study investigates the role of the two putative amine transmitters (norepinephrine and serotonin) in mediating the facilitatory action following locus coeruleus (LC) stimulation on hindlimb flexor and extensor monosynaptic reflexes (MSRs) in unanesthetized, decerebrate cats. When administered sequentially, in either order, methysergide (a serotonergic blocker) and prazosin (an alpha 1-adrenergic blocker) were observed to cause subtotal, decremental changes in the potentiation of gastrocnemius-soleus and common peroneal MSRs by stimuli applied in the LC. These changes were determined to be independent of the blood pressure changes induced by the aminergic blockers. These results support the hypothesis that the facilitation of the group Ia reflex transmission in cat spinal cord by stimulation of LC is mediated in part by alpha 1-noradrenergic and serotonergic mechanisms.

Adrenergic Fibers↗

Convergence and interaction of neck and macular vestibular inputs on locus coeruleus and subcoeruleus neurons.

Extracellular recordings were obtained in precollicular decerebrate cats from 90 neurons located in the noradrenergic area of the dorsal pontine tegmentum, namely in the dorsal (LCd, n = 24) and the ventral part (LC alpha, n = 40) of the locus coeruleus (LC) as well as in the locus subcoeruleus (SC, n = 26). Among these units of the LC complex, 13 were coerulospinal (CS) neurons antidromically identified following stimulation of the spinal cord at T12-L1. Some of these neurons showed the main physiological characteristics of the norepinephrine (NE)-containing LC neurons, i.e., a slow and regular resting discharge and a typical biphasic response to fore- and hindpaw compression consisting of a short burst of excitation followed by a period of quiescence, due, in part at least, to recurrent and/or lateral inhibition. Unit firing rate was analyzed under separate stimulation of macular vestibular, neck, or combined receptors by using sinusoidal rotation about the longitudinal axis at 0.15 Hz, +/- 10 degrees peak amplitude. Among the 90 LC-complex neurons, 60 (66.7%) responded with a periodic modulation of their firing rate to roll tilt of the animal and 67 (74.4%) responded to neck rotation. Convergence of macular and neck inputs was found in 52/90 (57.8%) LC-complex neurons; in these units, the gain and the sensitivity of the first harmonic of the response corresponded on the average to 0.34 +/- 0.45, SD, impulses.s-1.deg-1 and 3.55 +/- 2.82, SD, %/deg for the neck responses and to 0.23 +/- 0.29, SD, impulses.s-1.deg-1 and 3.13 +/- 3.04, SD, %/deg for the macular responses. In addition to these convergent units, 8/90 (8.9%) and 15/90 (16.7%) LC-complex units responded to selective stimulation either of macular or of neck receptors only. These units displayed a significantly lower response gain and sensitivity to animal tilt and neck rotation with respect to those obtained from convergent units. Most of the convergent LC-complex units were maximally excited by the direction of stimulus orientation, the first harmonic of responses showing an average phase lead of about +31.0 degrees with respect to neck position and +17.6 degrees with respect to animal position. Two populations of convergent neurons were observed. The first group of units (43/52, i.e., 82.7%) showed reciprocal ("out of phase") responses to the two inputs; moreover, most of these units were excited during side-down neck rotation, but inhibited during side-down animal tilt.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Responses of locus coeruleus and subcoeruleus neurons to sinusoidal neck rotation in decerebrate cat.

The electrical activity of 99 neurons located in the locus coeruleus-complex, namely in the dorsal (n = 26) and the ventral part of the locus coeruleus (n = 46) as well as the locus subcoeruleus (n = 27), has been recorded in precollicular decerebrate cats during sinusoidal displacement of the neck. This was achieved by rotation of the body about the longitudinal axis of the animal, while maintaining the head stationary. A proportion of these neurons showed some of the main physiological characteristics attributed to the noradrenergic locus coeruleus neurons, i.e. (i) a slow and regular resting discharge, and (ii) a typical biphasic response to fore and hindpaw compression consisting of short bursts of impulses followed by a period of quiescence, due at least in part to recurrent or lateral inhibition of the corresponding neurons. Moreover, 14 out of the 99 neurons were activated antidromically by stimulation of the spinal cord at T12 and L1, thus being considered as coeruleo- or subcoeruleospinal neurons. Among these locus coeruleus-complex neurons tested, 73 out of 99 (i.e. 73.7%) responded to neck rotation at the standard frequency of 0.15 Hz and at the peak amplitude of displacement of 10 degrees. In particular 40 of 73 units (i.e. 54.8%) were excited during side-down neck rotation and depressed during side-up rotation, while 18 of 73 units (i.e. 24.7%) showed the opposite pattern. In both instances the peak of the responses occurred with an average phase lead of +34.2 degrees for the extreme side-down or side-up neck displacement; however, the response gain (impulses/s per deg) was on the average more than two-fold higher in the former than in the latter group of units. The remaining 15 units (i.e. 20.5%) showed phase angle values which were intermediate between those of the two main populations. As to the coeruleo or subcoeruleospinal neurons, 11 of 14 units (78.6%) responded to the neck input, the majority (nine of 11 units, i.e. 81.8%) being excited during side-down neck rotation. Within the explored region, the proportion of responsive units was higher in the locus subcoeruleus (85.2%) than in the locus coeruleus, both dorsal and ventral (69.4%). Moreover, units located in the former structure showed on the average a response gain higher than that found in the latter structures. Similar results were also obtained from the population of locus subcoeruleus-complex neurons which fired at a low rate (less than or equal to 5.0 impulses/s).(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Responses of locus coeruleus neurons to convergent neck and vestibular inputs.

The locus coeruleus (LC) complex, located in the dorsolateral pontine tegmentum, is composed of noradrenergic and self-inhibitory adrenoceptive neurons, which project to broad regions of the brain, including the spinal cord. Experiments were performed in decerebrate cats to find out whether units which had the physiological characteristics of noradrenergic neurons (i.e., a slow and regular resting discharge and a typical response to a noxious stimulus consisting of a short burst of excitation followed by a silent period), received a convergent input from both labyrinth and neck receptors. Among 90 LC-complex units, 13 of which could be identified antidromically as coeruleospinal (CS) neurons following electrical stimulation of the spinal cord at T12-L1, 52 (57.8%) responded to roll tilt of the animal and neck rotation at 0.15 Hz, +/- 10 degrees. The responses were particularly related to the extreme animal and neck displacements. Most of these convergent neurons (43/52, i.e., 82.7%) showed reciprocal ('out of phase') responses to the two inputs, while only a few units (9/52, i.e., 17.3%) showed parallel ('in phase') responses. Moreover, the majority of the 'out of phase' units showed an increased discharge during side-up animal tilt and side-down neck rotation. These predominant response patterns were just opposite to those of the vestibulospinal (VS) neurons projecting to the same segments of the spinal cord. The response characteristics of the LC-complex neurons to combined neck and vestibular inputs elicited during head rotation usually corresponded to those predicted by a vectorial summation of the individual neck and labyrinth responses, as shown for the VS neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Cholinergic brainstem sites for gain control of vestibulospinal reflexes in cats.

Decerebrate cats were injected with carbachol into the locus coeruleus (LC) or with carbachol or bethanechol into the dorsal pontine reticular formation (pRF) of one side; recordings were made of the tonic contraction of forelimb extensor muscles of both sides and of their responses to sinusoidal roll tilt of the animal. Both drugs had similar effects when injected into the pRF: a decrease in the tonic contraction of limb extensors and a greatly enhanced amplitude and gain with slightly decreased phase lead in the responses to animal tilt of the forelimb extensor, triceps brachii, ipsilateral to the side of injection. Injected into the LC, carbachol produced a response opposite to the above: it increased the tonic contraction of limb extensors ipsilateral to the side of injection, but decreased the amplitude and gain of the EMG responses of limb extensor muscles to labyrinth stimulation induced by sinusoidal tilt. These findings did not depend on changes in posture since they were still observed when postural EMG activity was maintained constant by appropriate changes in static stretch of the muscle. Moreover, the magnitude of the effects increased in a dose-dependent manner. Results suggest that cholinergic activation of dorsal pRF neurons through muscarinic receptors increases the background discharge of medullary inhibitory reticulospinal (RS) system neurons, thus increasing their modulatory influence. Further, it is postulated that cholinergic activation of LC neurons would cause them to inhibit this tonic facilitatory drive by the pRF. Common to both sites of carbachol injection is the increase in phase lag of the EMG response of limb extensors to animal tilt.(ABSTRACT TRUNCATED AT 250 WORDS)

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Coerulospinal influence on recurrent inhibition of spinal motonuclei innervating antagonistic hindleg muscles of the cat.

The locus coeruleus's (LC's) effect on recurrent inhibition of gastrocnemius-soleus (GS) and common peroneal (CP) monosynaptic reflexes (MSRs) was demonstrated to exceed the concomitant facilitation, indicating the independency of LC's disinhibition and facilitation measures in this study. In contrast, the disinhibition effect correlated closely with the recurrently inhibited MSRs. The disinhibition phenomenon was also accompanied by progressive delay and diminution in the Renshaw cell field potential. Hence, the recovery of recurrently inhibited MSRs was probably due, in part at least, to the LC's inhibition of the related Renshaw cell activity. Furthermore, the site-specific, discordant changes in the disinhibition of GS, compared with CP MSRs, as revealed by tracking studies imply that representations of these antagonistic motonuclei may occupy different LC loci. Accordingly, the nonuniform disinhibition may be due to the activation of discrete aggregates of LC neurons which are responsible predominantly in controlling the recurrent inhibitory pathway belonging to one or the other of the antagonistic motonuclei. These findings support a differential LC inhibitory control of Renshaw cell activity, releasing the related motoneurones for the Ia synaptic transmission - a disinhibitory process that is crucial for the LC's independent control of the recurrent circuit of antagonistics extensor and flexor motoneurons.

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