Business-centric data solutions for safeguarding animal agriculture in the United States of America.

Business-centric solutions to data-related problems often yield the greatest positive impacts and improvements for private enterprises but are challenging to design and implement at scale within government agencies. The core mission of the Veterinary Services of the United States Department of Agriculture (USDA) Animal Plant Health Inspection Service is to safeguard animal agriculture in the United States of America, and effective data management underpins these efforts. As this agency works to assist data-driven decision-making in animal health management, it continues to use a blend of best practices from Federal Data Strategy initiatives and the International Data Management Association framework. This paper describes three case studies that focus on strategies to improve animal health data collection, integration, reporting and governance for animal health authorities. These strategies have enhanced the way USDA's Veterinary Services execute their mission and core operational activities for prevention, detection and early response to support disease containment and control.

S'agissant des problèmes en lien avec les données, les solutions centrées sur l'activité sont souvent celles qui génèrent le plus d'effets positifs et d'améliorations pour les entreprises du secteur privé, mais elles sont difficiles à concevoir et à mettre en oeuvre à grande échelle au sein des agences gouvernementales. Les Services vétérinaires du Service d'inspection de la santé animale et végétale du département américain de l'Agriculture (USDA) ont pour mission centrale de préserver les productions animales états-uniennes ; une gestion efficace des données vient soutenir cet effort. Dans leur action d'appui aux processus décisionnels de gestion de la santé animale fondés sur les données, ces Services recourent à une combinaison de bonnes pratiques mises en oeuvre aussi bien par les initiatives de la Stratégie fédérale sur les données que dans le cadre de l'Association internationale de gestion des données. Les auteurs décrivent trois études de cas sur des stratégies visant à améliorer la collecte, l'intégration, la notification et la gouvernance des données de santé animale afin de répondre aux besoins des autorités compétentes dans ce domaine. Ces stratégies ont permis aux Services vétérinaires de l'USDA de mieux s'acquitter de leur mission et d'améliorer leurs activités opérationnelles de prévention, de détection et de réaction rapide afin d'endiguer et contrôler les maladies.

Las soluciones eminentemente empresariales a problemas relacionados con los datos deparan con frecuencia los mejores frutos y resultados a la empresa privada, pero son difíciles de diseñar y aplicar a escala dentro de las administraciones públicas. Los Servicios Veterinarios adscritos al Servicio de Inspección Sanitaria de Animales y Plantas del Departamento de Agricultura de los Estados Unidos (USDA) tienen por principal cometido salvaguardar la producción animal estadounidense, labor que pasa en parte por una eficaz gestión de los datos. En su función de apoyo a la adopción de decisiones de gestión zoosanitaria basadas en los datos, este organismo sigue empleando una combinación de prácticas óptimas tomadas de iniciativas de la Estrategia Federal de Datos y de las pautas marcadas por la Asociación Internacional de Gestión de Datos. Los autores presentan y analizan tres ejemplos de estrategias para mejorar la obtención, integración, notificación y administración de datos zoosanitarios para las autoridades del ramo. Estas estrategias han conferido mayor eficacia a los Servicios Veterinarios del USDA en el cumplimiento de su misión y en la ejecución de sus principales actividades operativas de prevención, detección y pronta respuesta para ayudar a contener y combatir enfermedades.

[Current developments in measuring quality of life with instruments of the European organisation for research and treatment of cancer (EORTC)]. / Aktuelle Entwicklungen bei der Erfassung der Lebensqualität mit Instrumenten der European Organisation for Research and Treatment of Cancer (EORTC).

Since many years, the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group develops and validates measures for the assessment of quality of life in cancer patients, using high standards of methodology. These questionnaires are meant to be used primarily in clinical trials.As treatment strategies are changing and because of some -methodological criticism, the head and neck module EORTC QLQ-H&N35 is currently being revised and updated.In this paper, we will present the current state of work and other recent developments regarding the EORTC Quality of Life questionnaire development.

Prolactin and growth hormone release by morphine in the rat: different receptor mechanisms.

Concentrations of prolactin and growth hormone in the serum of rats were significantly increased by morphine. Dose response studies demonstrated that maximum prolactin release required lower doses of morphine than those needed for the maximum growth hormone response. Selective blockade of mu 1 (high affinity) opiate receptor with the irreversible antagonist naloxazone reduced morphine-induced peak concentrations of prolactin by 80 percent while increasing peak growth hormone levels by 250 percent. These results suggest different receptor mechanisms for the opiate modulation of the two hormones. The mu 1 (high affinity) receptor sites appear to mediate the morphine-induced release of prolactin but not growth hormone.

Translational regulation of somatostatin in cultured sympathetic neurons.

Coculture of sympathetic neurons with ganglion nonneuronal cells elevated levels of preprosomatostatin mRNA but did not alter neuronal synthesis, content, or release of somatostatin. Treatment of sympathetic neurons with culture medium conditioned by exposure to ganglion nonneuronal cells similarly elevated preprosomatostatin mRNA. Treatment with conditioned medium elevated somatostatin levels in pure neuronal cultures, but not in neurons cocultured with nonneuronal cells. Conditioned medium also failed to increase peptide levels in neurons cultured on a substratum of killed nonneuronal cells, despite a large increase in preprosomatostatin mRNA. These observations suggest that contact of sympathetic neurons with nonneuronal cell membranes inhibits the increase in peptide synthesis, but not the increase in preprosomatostatin mRNA after treatment with conditioned medium. Thus neuronal interactions with nonneuronal cells regulate somatostatin metabolism at both the mRNA and peptide levels. Regulatory effects on the mRNA and the peptide are separable and do not necessarily occur in parallel, and translational controls may be the rate-limiting factors.

The brain H3-receptor as a novel therapeutic target for vigilance and sleep-wake disorders.

Brain histaminergic neurons play a prominent role in arousal and maintenance of wakefulness (W). H(3)-receptors control the activity of histaminergic neurons through presynaptic autoinhibition. The role of H(3)-receptor antagonists/inverse agonists (H(3)R-antagonists) in the potential therapy of vigilance deficiency and sleep-wake disorders were studied by assessing their effects on the mouse cortical EEG and sleep-wake cycle in comparison to modafinil and classical psychostimulants. The H(3)R-antagonists, thioperamide and ciproxifan increased W and cortical EEG fast rhythms and, like modafinil, but unlike amphetamine and caffeine, their waking effects were not accompanied by sleep rebound. Conversely, imetit (H(3)R-agonist) enhanced slow wave sleep and dose-dependently attenuated ciproxifan-induced W, indicating that the effects of both ligands involve H(3)-receptor mechanisms. Additional studies using knockout (KO) mice confirmed the essential role of H(3)-receptors and histamine-mediated transmission in the wake properties of H(3)R-antagonists. Thus ciproxifan produced no increase in W in either histidine-decarboxylase (HDC, histamine-synthesizing enzyme) or H(1)- or H(3)-receptor KO-mice whereas its waking effects persisted in H(2)-receptor KO-mice. These data validate the hypothesis that H(3)R-antagonists, through disinhibition of H(3)-autoreceptors, enhancing synaptic histamine that in turn activates postsynaptic H(1)-receptors promoting W. Interestingly amphetamine and modafinil, despite their potent arousal effects, appear unlikely to depend on histaminergic mechanism as their effects still occurred in HDC KO-mice. The present study thus distinguishes two classes of wake-improving agents: the first acting through non-histaminergic mechanisms and the second acting via histamine and supports brain H(3)-receptors as potentially novel therapeutic targets for vigilance and sleep-wake disorders.

The role of complement in Alzheimer's disease pathology.

Complement proteins are integral components of amyloid plaques and cerebral vascular amyloid in Alzheimer brains. They can be found at the earliest stages of amyloid deposition and their activation coincides with the clinical expression of Alzheimer's dementia. This review will examine the origins of complement in the brain and the role of beta-amyloid peptide (Abeta) in complement activation in Alzheimer's disease, an event that might serve as a nidus of chronic inflammation. Pharmacology therapies that may serve to inhibit Abeta-mediated complement activation will also be discussed.

Immunoregulatory properties of synthetic peptides, fragments of a proline-rich polypeptide (PRP) from ovine colostrum.

It has been previously found that a proline-rich polypeptide (PRP) isolated from ovine colostrum has a regulatory effect on the immune response. A nonapeptide fragment Val-Glu-Ser-Tyr-Val-Pro-Leu-Phe-Pro was isolated from the chymotryptic digest of PRP. The nonapeptide showed biological activity similar to PRP. The determined amino acid sequence was now confirmed by synthesis. Synthetic nonapeptide as well as its C-terminal hexapeptide, Tyr-Val-Pro-Leu-Phe-Pro, showed biological activity similar to PRP and the nonapeptide obtained from PRP.

Immunoregulatory activity of substance P fragments.

The C-terminal SP7-11 pentapeptide (Phe-Phe-Gly-Leu-Met-NH2) was found to suppress in vitro the immune response in a dose of 1-5 micrograms/ml. It produced also a distinct immunosuppression in vivo, by both per os and intraperitoneal, applications. In contrast, the N-terminal SP1-4 fragment (Arg-Pro-Lys-Pro) suppressed the response at a dose of 0.1 microgram/ml, but stimulated it slightly at higher doses (1-5 micrograms/ml). A structural analog of SP1-4 (Gly-Pro-Arg-Pro tetrapeptide) was found to be a strong immunosuppressor at a dose of 5 micrograms/ml, indicating the importance of N-terminal basic residue for the immunoregulatory activity of intact SP.

Disruption of endocrine rhythms in sleeping sickness with preserved relationship between hormonal pulsatility and the REM-NREM sleep cycles.

In human African trypanosomiasis (sleeping sickness), sleep and wake episodes are sporadically distributed throughout the day and the night. To determine whether these sleep disturbances affect the 24-h hormone profiles and the normal relationships between hormone pulsatility and sleep stages, polygraphic sleep recordings and concomitant hormone profiles were obtained in 6 African patients with sleeping sickness and in 5 healthy African subjects selected from Abidjan on the Ivory Coast. Polysomnographic recordings were continuous, and blood was taken every 10 min throughout the 24-h period. Plasma was analyzed for cortisol, prolactin, and plasma renin activity (PRA). The 24-h rhythm of cortisol, considered to be an endogenous circadian rhythm, was attenuated in all of the patients except one. However, as in normal subjects, slow wave sleep (SWS) remained associated with the declining phases of the cortisol secretory episodes. Prolactin and PRA profiles, which are strongly influenced by the sleep-wake cycle, did not manifest the nocturnal increase normally associated with the sleep period; instead, they reflected a sporadic distribution of the sleep and wake episodes throughout the 24-h period. In patients with sleeping sickness as in normal subjects, rapid eye movement (REM) sleep began during the descending phases of prolactin pulses. In both groups, PRA reflected the sleep stage distribution with non REM (NREM) sleep occurring during the ascending phases and REM sleep during the descending phases of the PRA oscillations. However, in sleeping sickness patients, the marked sleep fragmentation often did not allow sufficient time for PRA to increase significantly, as is normally the case in subjects with regular NREM-REM sleep cycles. These results demonstrate that, together with the disruption of the sleep-wake cycle, there are profound differences in the temporal organization of the 24-h hormone profiles in humans with African trypanosomiasis. However, the relationship between hormonal pulses and specific sleep stages persists, indicating the existence of a robust link between hormonal release and the internal sleep structure.

The cholinergic deficit coincides with Abeta deposition at the earliest histopathologic stages of Alzheimer disease.

Effective therapeutic intervention in Alzheimer disease (AD) will be most effective if it is directed at early events in the pathogenic sequence. The cholinergic deficit may be such an early event. In the present study, the brains of 26 subjects who had no history of cognitive loss and who were in early histopathologic stages of AD (average Braak stage less than II) were examined at autopsy to determine whether a cortical cholinergic decrement was associated with Abeta concentration or deposition. In the superior frontal and inferior temporal gyri, the choline acetyltransferase (ChAT) activity of plaque-containing cases was significantly decreased (p < 0.05, unpaired, two-tailed t-tests), measuring 70.9% and 79.5%, respectively, relative to plaque-free cases. In the inferior temporal gyrus, Spearman's rank correlation analysis showed that ChAT activity had a significant inverse correlation with Abeta concentration (p = 0.075; r = -0.3552). The results indicate that the cholinergic deficit is established at an early histopathologic stage of AD, before the onset of clinical symptoms.

Relationships between intact parathyroid hormone 24-hour profiles, sleep-wake cycle, and sleep electroencephalographic activity in man.

To determine whether the 24-h intact PTH (iPTH) profile is influenced by the sleep-wake cycle, and whether iPTH pulses show a temporal relationship with internal sleep structure, eight normal young men were studied during 24 h under basal conditions, once with normal nighttime sleep from 2300-0700 h and once after a night of sleep deprivation followed by an 8-h period of daytime sleep from 0700-1500 h. During the 8-h nighttime sleep period, mean iPTH levels were significantly increased by +13% and mean iPTH pulse amplitudes by +31% as compared with the 8-h subsequent waking periods. During the 8 h of total sleep deprivation, mean iPTH levels were not significantly different from the corresponding period in nighttime sleep condition, but mean iPTH pulse amplitudes were significantly lower (P < 0.01). The 8-h daytime sleep period was associated with increased mean iPTH levels and mean iPTH pulse amplitudes (+15% and +57%, respectively, as compared with the corresponding period in nighttime sleep condition). The number of pulses was similar in both experimental series and was not influenced by sleep or by time of day. Analysis of coincidence between iPTH pulses, plasma ionized calcium and plasma phosphate pulses, and slow wave sleep, as well as with rapid eye movement sleep episodes, did not reveal any significant association. Cross-correlation analysis between iPTH, plasma ionized calcium, and plasma phosphate fluctuations during sleep also showed no systematic association. Seven other subjects were studied during a nighttime sleep period in which temporal relationships between iPTH and internal sleep structure were reevaluated using spectral analysis of the sleep electroencephalogram. Cross-correlation analysis between iPTH levels and delta-relative power fluctuations showed nonsignificant results, which confirms the lack of relationship with slow wave sleep. This study demonstrates that the iPTH 24-h profile is influenced by sleep processes with a weak circadian component. However, iPTH pulses are not temporally linked with sleep electroencephalographic activity nor with calcemia and phosphatemia fluctuations. This evidence raises questions about the origin of iPTH pulses.

Application of a microseparation technique allowing for extensive marker studies on small bone marrow specimens.

The characterization of surface and intracellular markers of hematopoietic cells by immunocytochemical methods is widely used. While examination of cells of the peripheral blood can easily be performed, investigations of bone marrow cells can be hampered by technical difficulties in labeling routine marrow smears or by limited size of specimens required for cytocentrifugation. A simple and highly efficient method for isolation of bone marrow cells by a microseparation technique is described. Only two to three drops of a routine bone marrow aspirate are necessary for preparation of up to 100 cytocentrifuge slides thereby exceeding separation efficiency of conventional gradient centrifugation by three- to more than four-fold. The application of the method for marker studies on normal marrow and marrow from patients with hematologic malignancies is exemplified.

Twenty-four-hour profiles of plasma renin activity in relation to the sleep-wake cycle.

OBJECTIVE: To evaluate the relative contribution of sleep and the endogenous circadian rhythmicity in producing the 24-h variations in the plasma renin activity. METHODS: Ten normal young men were studied, under basal conditions with normal nocturnal sleep from 2300-0700 h and once after a night of total sleep deprivation followed by 8 h daytime sleep from 0700 to 1500 h. Plasma renin activity was measured every 10 min for 24 h and the profiles were analysed using the pulse detection program ULTRA. RESULTS: During the 8 h night-time sleep a significant increase in the mean plasma renin activity levels occurred compared with the subsequent 8-h waking periods. After the shift in the sleep period, a sleep-associated increase was clearly apparent during the daytime hours. The number of the amplitude of the oscillations, linked to the non-rapid eye movement-rapid eye movement sleep cycles, increased during sleep (at whatever time it occurred), and were dependent on the regularity and the length of the sleep cycles. In awake subjects the plasma renin activity generally fluctuated in a more damped and irregular manner, but occasionally the plasma renin activity oscillated at a regular periodicity with two dominant peaks centred around 100 and 50 min. CONCLUSION: These results demonstrate that the 24-h plasma renin activity variations are not circadian in nature but are related to sleep processes, which create the nycthemeral rhythm by increasing both the frequency and the amplitude of the oscillations.

Kynurenic acid derivatives inhibit the binding of nerve growth factor (NGF) to the low-affinity p75 NGF receptor.

The ability of a series of substituted kynurenic acids, thienopyridinonecarboxylic acids, and related compounds to inhibit the binding of nerve growth factor (NGF) to the p75 NGF receptor (NGFR) was evaluated in a radioligand binding assay that utilized a biotinylated derivative of the extracellular domain of p75 NGFR (p75ext) fixed to streptavidin-coated plastic wells. Two compounds, 6-aminokynurenic acid (5h) and the 3-methyl ester of 4,7-dihydro-2-methyl-7-oxothieno[3,2-b]pyridine-3,5-dicarboxylic acid (16), were found to inhibit the binding of [125I]NGF to p75ext with IC50 values in the low micromolar range. Other amino-substituted kynurenic acids also possessed activity at slightly higher concentrations. Several structural features seem to be essential, including the carboxylic acid, a polar group on the benzene ring (or thiophene ring, in the case of analogues of 16), and the C-4 carbonyl group in the pyridinone ring. These compounds were also found to inhibit the binding of [125I]NGF to its receptors in membranes from PC12 cells (which express p75 as well as trka receptors for NGF) and DG44-CHO cells (transfected with full length p75 NGFR). The available data for 5h and 16 do not allow the determination of whether the effects of these compounds are mediated by their interaction with NGF or the NGF receptors.

Therapeutic intervention in dementia.

The search for novel therapeutics for human cognitive disorders has intensified. Neurotransmitter replacement therapies represent a short-term hope for treating cognitive dysfunction associated with Alzheimer's disease (AD). AD, however, is clearly a neurodegenerative disease and is characterized by a loss of synaptic elements. Ultimately, synaptic loss must be halted to alter the disease course. Agents mimicking or modulating the actions of neurotrophic factors may be useful. They may restore lost function and exert anabolic effects on existing neurons, making treated cells less susceptible to neurotoxic insult (i.e., excitotoxicity, oxidative stress, etc.). Intervening in the biogenesis of amyloid plaques and blunting local inflammatory responses may provide the ultimate treatment for AD. The success of any treatment, however, rests on early diagnosis. Early intervention in the neurodegenerative disease process will be required. Without early intervention, the risk of maintaining patients in a premorbid state is high. Therefore, it is likely that no single approach will provide optimal therapy for the AD patient and multifactorial treatment strategies may be required.

Comparative effect of night and daytime sleep on the 24-hour cortisol secretory profile.

To determine whether cortisol secretion interacts with daytime sleep in a similar manner to that reported for night sleep, 14 healthy young men were studied during two 24-hour cycles. During one cycle they slept during the night, during the other the sleep period was delayed by 8 hours. Secretory rates were calculated by a deconvolution procedure from plasma cortisol, measured at 10-minute intervals. The amount of cortisol secreted during night sleep was lower than during the corresponding period of sleep deprivation (12.7 +/- 1.1 vs. 16.3 +/- 1.6 mg; p < 0.05), but daytime sleep beginning at the habitual time of morning awakening failed to inhibit cortisol secretion significantly. There was no difference between the amount of cortisol secreted from 0700 to 1500 hours in sleeping subjects and in subjects who were awake during the same period of time (24.2 +/- 1.5 vs. 22.5 +/- 1.4 mg). Even if the comparison between sleeping and waking subjects was restricted to the period 0700-1100 hours or 0700-0900 hours, no significant difference was found. Neither secretory pulse amplitude nor frequency differed significantly in either period. However, detailed analysis of the secretory rates in day sleepers demonstrated a transient decrease in cortisol secretion at about the time of sleep onset, which began 10 minutes before and lasted 20 minutes after falling asleep. Spontaneous or provoked awakenings had a determining influence on the secretory profiles. Ten to 20 minutes after awakening from either night or day sleep cortisol secretion increased significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Prolactin secretion and sleep.

To clarify the relationship between prolactin (PRL) secretion and sleep, three experimental procedures were employed and secretory rates were estimated from plasma levels using a deconvolution procedure. Eight healthy young men participated in two 24-hour studies, one using normal night sleep and one using delayed sleep, to determine the influence of sleep as a whole on the PRL rhythm. Another group of 24 subjects underwent a 1-night study to investigate the relationship between PRL secretion and the internal sleep structure. The influence of sleep quality was studied in two more groups of eight subjects. Secretory rates were calculated by deconvolution from plasma PRL measured at 10-minute intervals. Sleep was recorded polygraphically in all experiments. PRL secretory pulses occurred throughout the 24-hour cycle without significant variation in frequency, but with enhanced pulse amplitude for both night and day sleep periods. Sleep onset was rapidly followed by an increase in secretion, and awakenings coincided with an immediate offset of active secretion. Analyzing the association between secretory pulses and sleep stages demonstrated that PRL secretory rate is low at the time of rapid eye movement sleep onset. Sleep quality appeared not to affect the PRL secretory profile. These results confirmed that PRL secretion is enhanced during the whole sleep period, as inferred from plasma levels. Considering secretory pulses provides a precise determination of the temporal relations between PRL and sleep structure and demonstrates that occasionally poor sleep does not influence PRL secretion in normal humans.

Temporal relationship between prolactin secretion and slow-wave electroencephalic activity during sleep.

It is well established that plasma prolactin (PRL) concentrations exhibit a sleep-dependent pattern, with the highest levels occurring during sleep and the lowest during waking. Still, controversy exists concerning an association between rapid eye movement (REM) and non-REM sleep cycles and plasma PRL pulses. These studies were all based on conventional scoring of sleep stages. In the present study, plasma PRL concentrations were analyzed at 10-minute intervals in 10 subjects during the night when sleeping. PRL secretory rates were calculated by a deconvolution procedure. Spectral parameters of sleep electroencephalographic (EEG) recordings were analyzed together with PRL secretion using cross-correlation. Slow-wave activity of the EEG and PRL secretion ran parallel in all individuals. Conversely, alpha and beta bands and the EEG mean frequency were inversely proportional to PRL secretion. In 9 of the 10 subjects studied, PRL secretion was concomitant with delta waves or lagged behind by 10-20 minutes, depending on subjects, with maximum cross-correlation coefficients ranging between 0.40 and 0.67. This temporal relationship between PRL secretion and delta waves was further assessed by a pulse-by-pulse analysis based on the calculation of probability levels after computer simulations. Nine of the 10 subjects displayed significant concomitance between delta wave activity and PRL secretory oscillations. These results demonstrate that PRL secretion during sleep is coupled to delta waves in young healthy men.

Pathophysiology of human circadian rhythms.

The 24 h profiles of hormonal secretions represent a good model for the study of the human circadian system. Diurnal hormonal variations generally reflect the modulation of ultradian or pulsatile release at 1-2 h intervals by signals occurring at nearly 24 h periods and result from the interaction of an internal timekeeping system--or circadian clock--with the sleep-wake homeostasis and various environmental factors, including the light-dark cycle, periodic changes in activity levels and the meal schedule. This temporal organization is altered in many pathophysiological conditions, including ageing, sleep loss, night or shift work, jet lag, affective disorders and endocrine diseases. Both photic and non-photic stimuli may affect the regulation of the circadian pacemaker and, therefore, the diurnal pattern of hormonal secretions. Appropriately timed stimuli may induce either a phase-advance or a phase-delay of the circadian clock, according to the timing of administration. Phase-shifting effects have been shown in humans for light and for dark pulses, physical exercise, melatonin and melatonin agonists, and benzodiazepine hypnotics. These results open new perspectives for the treatment of a variety of disorders involving dysregulation of the circadian rhythmicity.

Differences in the effects of membrane depolarization on levels of preprosomatostatin mRNA and tyrosine hydroxylase mRNA in rat sympathetic neurons in vivo and in culture.

Regulation of preprosomatostatin mRNA and tyrosine hydroxylase mRNA were examined in sympathetic neurons of the rat superior cervical ganglion (SCG). Surgical denervation of the adult SCG increased ganglion levels of preprosomatostatin (SS) mRNA more than 11-fold, and levels of the mRNA remained elevated 14 days after surgery. By contrast, denervation decreased levels of tyrosine hydroxylase (TH) mRNA. Potassium- or veratridine-induced membrane depolarization of cultured neonatal sympathetic neurons decreased levels of SS mRNA but elevated levels of TH mRNA. Sodium channel blockade with tetrodotoxin prevented the effects of veratridine on SS and TH mRNAs. In toto these observations suggest that transsynaptic nerve impulse activity and sympathetic neuron membrane depolarization decrease SS synthesis but increase TH synthesis at the mRNA level. Thus nerve impulse activity may alter the relative levels of different transmitters co-expressed in the same neuronal population by inhibiting levels of some species of mRNA while simultaneously stimulating levels of others.