Délégation Régionale Auvergne-Rhône-Alpes

Global biodiversity in freshwater and the oceans is declining at high rates. Reliable tools for assessing and monitoring aquatic biodiversity, especially for rare and secretive species, are important for efficient and timely management. Recent advances in DNA sequencing have provided a new tool for species detection from DNA present in the environment. In this study, we tested whether an environmental DNA (eDNA) metabarcoding approach, using water samples, can be used for addressing significant questions in ecology and conservation. Two key aquatic vertebrate groups were targeted: amphibians and bony fish. The reliability of this method was cautiously validated in silico, in vitro and in situ. When compared with traditional surveys or historical data, eDNA metabarcoding showed a much better detection probability overall. For amphibians, the detection probability with eDNA metabarcoding was 0.97 (CI = 0.90-0.99) vs. 0.58 (CI = 0.50-0.63) for traditional surveys. For fish, in 89% of the studied sites, the number of taxa detected using the eDNA metabarcoding approach was higher or identical to the number detected using traditional methods. We argue that the proposed DNA-based approach has the potential to become the next-generation tool for ecological studies and standardized biodiversity monitoring in a wide range of aquatic ecosystems.

PET was used to map brain regions that are associated with the observation of meaningful and meaningless hand actions. Subjects were scanned under four conditions which consisted of visually presented actions. In each of the four experimental conditions, they were instructed to watch the actions with one of two aims: to be able to recognize or to imitate them later. We found that differences in the meaning of the action, irrespective of the strategy used during observation, lead to different patterns of brain activity and clear left/right asymmetries. Meaningful actions strongly engaged the left hemisphere in frontal and temporal regions while meaningless actions involved mainly the right occipitoparietal pathway. Observing with the intent to recognize activated memory-encoding structures. In contrast, observation with the intent to imitate was associated with activation in the regions involved in the planning and in the generation of actions. Thus, the pattern of brain activation during observation of actions is dependent both on the nature of the required executive processing and the type of the extrinsic properties of the action presented.

This paper describes the OpenViBE software platform which enables researchers to design, test, and use brain–computer interfaces (BCIs). BCIs are communication systems that enable users to send commands to computers solely by means of brain activity. BCIs are gaining interest among the virtual reality (VR) community since they have appeared as promising interaction devices for virtual environments (VEs). The key features of the platform are (1) high modularity, (2) embedded tools for visualization and feedback based on VR and 3D displays, (3) BCI design made available to non-programmers thanks to visual programming, and (4) various tools offered to the different types of users. The platform features are illustrated in this paper with two entertaining VR applications based on a BCI. In the first one, users can move a virtual ball by imagining hand movements, while in the second one, they can control a virtual spaceship using real or imagined foot movements. Online experiments with these applications together with the evaluation of the platform computational performances showed its suitability for the design of VR applications controlled with a BCI. OpenViBE is a free software distributed under an open-source license.

The study of pain in awake animals raises ethical, philosophical, and technical problems. We review the ethical standards for studying pain in animals and emphasize that there are scientific as well as moral reasons for keeping to them. Philosophically, there is the problem that pain cannot be monitored directly in animals but can only be estimated by examining their responses to nociceptive stimuli; however, such responses do not necessarily mean that there is a concomitant sensation. The types of nociceptive stimuli (electrical, thermal, mechanical, or chemical) that have been used in different pain models are reviewed with the conclusion that none is ideal, although chemical stimuli probably most closely mimic acute clinical pain. The monitored reactions are almost always motor responses ranging from spinal reflexes to complex behaviors. Most have the weakness that they may be associated with, or modulated by, other physiological functions. The main tests are critically reviewed in terms of their sensitivity, specificity, and predictiveness. Weaknesses are highlighted, including 1) that in most tests responses are monitored around a nociceptive threshold, whereas clinical pain is almost always more severe; 2) differences in the fashion whereby responses are evoked from healthy and inflamed tissues; and 3) problems in assessing threshold responses to stimuli, which continue to increase in intensity. It is concluded that although the neural basis of the most used tests is poorly understood, their use will be more profitable if pain is considered within, rather than apart from, the body's homeostatic mechanisms.

Despite its critical sociobiological importance, the brain processing of visual sexual stimuli has not been characterized precisely in human beings. We used Positron Emission Tomography (PET) to investigate responses of regional cerebral blood flow (rCBF) in nine healthy males presented with visual sexual stimuli of graded intensity. Statistical Parametric Mapping was used to locate brain regions whose activation was associated with the presentation of the sexual stimuli and was correlated with markers of sexual arousal. The claustrum, a region whose function had been unclear, displayed one of the highest activations. Additionally, activations were recorded in paralimbic areas (anterior cingulate gyrus, orbito-frontal cortex), in the striatum (head of caudate nucleus, putamen), and in the posterior hypothalamus. By contrast, decreased rCBF was observed in several temporal areas. Based on these results, we propose a model of the brain processes mediating the cognitive, emotional, motivational, and autonomic components of human male sexual arousal.

Mouse embryonic stem cells were induced to differentiate in culture with retinoic acid. Putative precursors of neurons and glial cells (nestin-positive cells) were clearly identified as early as three days after the onset of differentiation. At day 6, neuron-like cells could be clearly identified, either as isolated cells or as cellular networks. Some of these cells were positive for astrocyte- or oligodendrocyte-specific antigens (GFAP or O4 antigens, respectively). Other cells were positive for neuron-specific antigens (cytoskeleton proteins MAP2, MAP5 and NF200, as well as synaptophysin). Some neuronal-like cells were also positive for acetylcholinesterase activity or glutamic acid decarboxylase expression, indicating that ES cells could differentiate into GABAergic and possibly cholinergic neurons. Electrophysiological analyses performed in voltage clamp conditions showed that cell membranes contained voltage-dependent channels. Overshooting action potentials could be triggered by current injection. Taken together, these data provide evidence that embryonic stem cells can differentiate first into neuron-glia progenitors, and later into glial cells and functional neurons, in vitro. This technique provides an unique system to study early steps of neuronal differentiation in vitro.

The role of lysophosphatidic acid (LPA) in cancer is poorly understood. Here we provide evidence for a role of LPA in the progression of breast cancer bone metastases. LPA receptors LPA(1), LPA(2), and LPA(3) were expressed in human primary breast tumors and a series of human breast cancer cell lines. The inducible overexpression of LPA(1) in MDA-BO2 breast cancer cells specifically sensitized these cells to the mitogenic action of LPA in vitro. In vivo, LPA(1) overexpression in MDA-BO2 cells enhanced the growth of subcutaneous tumor xenografts and promoted bone metastasis formation in mice by increasing both skeletal tumor growth and bone destruction. This suggested that endogenous LPA was produced in the tumor microenvironment. However, MDA-BO2 cells or transfectants did not produce LPA. Instead, they induced the release of LPA from activated platelets which, in turn, promoted tumor cell proliferation and the LPA(1)-dependent secretion of IL-6 and IL-8, 2 potent bone resorption stimulators. Moreover, platelet-derived LPA deprivation in mice, achieved by treatment with the platelet antagonist Integrilin, inhibited the progression of bone metastases caused by parental and LPA(1)-overexpressing MDA-BO2 cells and reduced the progression of osteolytic lesions in mice bearing CHO-beta3wt ovarian cancer cells. Overall, our data suggest that, at the bone metastatic site, tumor cells stimulate the production of LPA from activated platelets, which enhances both tumor growth and cytokine-mediated bone destruction.

1. Healthy subjects actually performed and mentally simulated a leg exercise at two levels of work (15 and 19 kg loads). Heart rate, respiration rate and end-tidal PCO2 were measured in both conditions. In addition, muscular metabolism was simultaneously measured using 31P nuclear magnetic resonance (NMR) spectroscopy. 2. During actual exercise, heart and respiration rates increased, first abruptly and then gradually in relation to the level of work. End-tidal PCO2 was unaltered. NMR spectra showed a drop in phosphocreatine (PCr) and an increase in inorganic phosphate (Pi) concentrations. Intracellular pH fell to 6.65 at maximal effort with a 19 kg load. 3. During mental simulation, both heart and ventilatory rate increased immediately after mental exercise was begun. This increase was proportional to the amount of simulated exercise. Heart rate remained about 25% below the level observed during actual exercise. The increase in respiration rate, by contrast, was more marked than during actual exercise. Finally, end-tidal PCO2 decreased progressively to about 18% of the resting value. 4. During mental simulation, NMR spectra were unchanged with respect to the resting values. 5. Subjects rated their sensation of fatigue using an analog rating scale, during both actual exercise and mental simulation. During mental exercise, the sensation of fatigue was greater with the 19 kg load than with the 15 kg load. 6. These results demonstrate that mental simulation of action can activate heart and respiration control mechanisms. They suggest that autonomic activation during imagined action pertains to the more general phenomenon of preparation for action.

A number of lines of evidence suggest that, in the macaque monkey, inferior parietal and inferotemporal cortices process different types of visual information. It has been suggested that visual information reaching these two subdivisions follows separate pathways from the striate cortex through the prestriate cortex. We examined directly this possibility by placing injections of the retrograde fluorescent tracers, fast blue and diamidino yellow, in inferior parietal and inferotemporal cortex and examining the spatial pattern of cortical areas containing labeled cells in two-dimensional reconstructions of the cortex. The results of injections in inferotemporal cortex show that TEO receives afferents from areas V2, ventral V3, V3A, central V4, V4t, and DPL in prestriate cortex and from areas IPa, PGa, and FST in the superior temporal sulcus (STS). Area TEp receives afferents only from V4 in prestriate cortex and from IPa, PGa, and FST in the anterior STS. Area TEa receives no prestriate input and is innervated by IPa, PGa, FST, and TPO in the anterior STS. The results of injections in inferior parietal cortex demonstrate that POa receives afferents from dorsal V3, V3A, peripheral V4, DPL, and PO in prestriate cortex, from MST and *VIP and from IPa, PGa, TPO, and FST in anterior STS. Area PGc (corresponding to 7a) is innervated by PO, MST, and by TPO in the anterior STS. Examination of the two-dimensional reconstructions of the pattern of labeling after combined injections of fast blue and diamidino yellow in areas POa and TEO revealed that these areas are principally innervated by different prestriate areas. Only a small region, centered on area V3A and extending into V4 and DPL, contained cells labeled by either injection as well as a small number of double-labeled cells. In contrast, areas POa and TEO receive afferents from extensive common regions in the anterior STS corresponding to areas IPa, PGa, and FST. These results directly demonstrate that visual information from the striate cortex reaches inferior parietal and inferotemporal cortices through largely separate prestriate cortical pathways. On the other hand, both parietal and inferotemporal cortices receive common inputs from extensive regions in the anterior STS which map play a role in linking the processing occurring in these two cortical subdivisions of the visual system.

Connections of the posterior parietal cortex (area 7) with subcortical structures related to the vestibulo-ocular function were studied on four macaque monkeys by using anterograde and retrograde tracer. Wheat germ agglutinin (WGA)-horseradish peroxidase (HRP) or tritiated amino acids were injected into the posterior part of area 7, including the caudal end of the superior bank of both the superior temporal sulcus and the lateral sulcus. The posterior parietal cortex was found to be reciprocally connected with three different ipsilateral thalamic nuclei: the nucleus ventralis posterior inferior, the magnocellular part of the medial geniculate nucleus, and some intralaminar nuclei. Through these connections, area 7 might control the vestibulo-ocular response (VOR) by modulating the ascending vestibular information. This cortical area 7 also projects to the ipsilateral intermediate and deep layers of the superior colliculus and to several ipsilateral pontine nuclei. The dorsolateral pontine nucleus is of particular interest because it is known to be related to smooth pursuit eye movements. Cortical area 7 also was seen to project to the accessory nucleus of Darkschewitsch, to all the vestibular nuclei, and to the nucleus propositus hypoglossi; the last two projections were found to be bilateral with a greater ipsilateral contribution. Efferents from posterior parietal cortex are directed to precise regions within the vestibular nuclei that are specifically involved in vestibulo-ocular reflex, or that are in turn connected with brainstem structures implicated in smooth pursuit eye movements. These connections are consistent with the posterior parietal cortex exerting a multilevel influence on the different systems dealing with eye-head movement coordination.

Dendritic morphology has a profound impact on neuronal information processing. The overall extent and orientation of dendrites determines the kinds of input a neuron receives. Fine dendritic appendages called spines act as subcellular compartments devoted to processing synaptic information, and the dendritic branching pattern determines the efficacy with which synaptic information is transmitted to the soma. The acquisition of a mature dendritic morphology depends on the coordinated action of a number of different extracellular factors. Here we discuss this evidence in the context of dendritic development in the cerebral cortex. Soon after migrating to the cortical plate, neurons extend an apical dendrite directed toward the pial surface. The oriented growth of the apical dendrite is regulated by Sema3A, which acts as a dendritic chemoattractant. Subsequent dendritic development involves signaling by neurotrophic factors and Notch, which regulate dendritic growth and branching. During postnatal development the formation and stabilization of dendritic spines are regulated in part by patterns of synaptic activity. These observations suggest that extracellular signals play an important role in regulating every aspect of dendritic development and thereby exert a critical influence on cortical connectivity.

Working memory involves the short-term storage and manipulation of information necessary for cognitive performance, including comprehension, learning, reasoning and planning. Although electroencephalogram (EEG) rhythms are modulated during working memory, the temporal relationship of EEG oscillations with the eliciting event has not been well studied. In particular, the dynamics of the neural network supporting memory processes may be best captured in induced oscillations, characterized by a loose temporal link with the stimulus. In order to differentiate induced from evoked functional processes, the present study proposes a time-frequency analysis of the 3 to 30 Hz EEG oscillatory activity in a verbal n-back working memory paradigm. Control tasks were designed to identify oscillatory activity related to stimulus presentation (passive task) and focused attention to the stimulus (detection task). Evoked theta activity (4-8 Hz) phase-locked to the visual stimulus was evidenced in the parieto-occipital region for all tasks. In parallel, induced theta activity was recorded in the frontal region for detection and n-back memory tasks, but not for the passive task, suggesting its dependency on focused attention to the stimulus. Sustained induced oscillatory activity was identified in relation to working memory in the theta and beta (15-25 Hz) frequency bands, larger for the highest memory load. Its late occurrence limited to nonmatched items suggests that it could be related to item retention and active maintenance for further task requirements. Induced theta and beta activities displayed respectively a frontal and parietal topographical distribution, providing further functional information on the fronto-posterior network supporting working memory.

The human brain is expert in analyzing rapidly and precisely facial features, especially emotional expressions representing a powerful communication vector. The involvement of insula in disgust recognition has been reported in behavioral and functional imaging studies. However, we do not know whether specific insular fields are involved in disgust processing nor what the processing time course is. Using depth electrodes implanted during presurgical evaluation of patients with drug-refractory temporal lobe epilepsy, we recorded intracerebral event-related potentials to human facial emotional expressions, that is, fear, disgust, happiness, surprise, and neutral expression. We studied evoked responses in 13 patients with insular contacts to specify the insular fields involved in disgust processing and assess the timing of their activation. We showed that specific potentials to disgust beginning 300 milliseconds after stimulus onset and lasting 200 milliseconds were evoked in the ventral anterior insula in four patients. The occurrence and latency of event-related potentials to disgust in the ventral anterior insula were affected by selective attention. The analysis of spatial and temporal characteristics of insular responses to disgust facial expression lead us to underline the crucial role of ventral anterior insula in the categorization of facial emotional expressions, particularly the disgust.

In the last few years, the study of environmental DNA (eDNA) has drawn attention for many reasons, including its advantages for monitoring and conservation purposes. So far, in aquatic environments, most of eDNA research has focused on the detection of single species using species-specific markers. Recently, species inventories based on the analysis of a single generalist marker targeting a larger taxonomic group (eDNA metabarcoding) have proven useful for bony fish and amphibian biodiversity surveys. This approach involves in situ filtering of large volumes of water followed by amplification and sequencing of a short discriminative fragment from the 12S rDNA mitochondrial gene. In this study, we went one step further by investigating the spatial representativeness (i.e. ecological reliability and signal variability in space) of eDNA metabarcoding for large-scale fish biodiversity assessment in a freshwater system including lentic and lotic environments. We tested the ability of this approach to characterize large-scale organization of fish communities along a longitudinal gradient, from a lake to the outflowing river. First, our results confirm that eDNA metabarcoding is more efficient than a single traditional sampling campaign to detect species presence, especially in rivers. Second, the species list obtained using this approach is comparable to the one obtained when cumulating all traditional sampling sessions since 1995 and 1988 for the lake and the river, respectively. In conclusion, eDNA metabarcoding gives a faithful description of local fish biodiversity in the study system, more specifically within a range of a few kilometers along the river in our study conditions, i.e. longer than a traditional fish sampling site.

1. In natural conditions, gaze (i.e., eye + head) orientation is a complex behavior involving simultaneously the eye and head motor systems. Thus one of the key problems of gaze control is whether or not the vestibuloocular reflex (VOR) elicited by head rotation and saccadic eye movement linearly add. 2. Kinematics of human gaze saccades within the oculomotor range (OMR) were quantified under different conditions of head motion. Saccades were visually triggered while the head was fixed or passively moving at a constant velocity (200 deg/s) either in the same direction as, or opposite to, the saccade. Active eye-head coordination was also studied in a session in which subjects were trained to actively rotate their head at a nearly constant velocity during the saccade and, in another session, during natural gaze responses. 3. When the head was passively rotated toward the visual target, both maximum and mean gaze velocities increased with respect to control responses with the head fixed; these effects increased with gaze saccade amplitude. In addition, saccade duration was reduced so that corresponding gaze accuracy, although poorer than for control responses, was not dramatically affected by head motion. 4. The same effects on gaze velocity were present during active head motion when a constant head velocity was maintained throughout saccade duration, and gaze saccades were as accurate as with the head fixed. 5. During natural gaze responses, an increased gaze velocity and a decreased saccade duration with respect to control responses became significant only for gaze displacement larger than 30 degrees, due to the negligible contribution of head motion for smaller responses. 6. When the head was passively rotated in the opposite direction to target step, gaze saccades were slower than those obtained with the head fixed; but their average accuracy was still maintained. 7. These results confirm a VOR inhibition during saccadic eye movements within the OMR. This inhibition, present in all 16 subjects studied, ranged from 40 to 96% (for a 40 degree target step) between subjects and increased almost linearly with target step amplitude. Furthermore, the systematic difference between instantaneous VOR gain estimated at the time of maximum gaze velocity and mean VOR gain estimated over the whole saccadic duration indicates a decay of VOR inhibition during the ongoing saccade. 8. A simplified model is proposed with a varying VOR inhibition during the saccade. It suggests that VOR inhibition is not directly controlled by the saccadic pulse generator.(ABSTRACT TRUNCATED AT 400 WORDS)

Abstract Retinal projections and visual thalamo‐cortical connections were studied in the subterranean mole rat, belonging to the superspecies Spalax ehrenbergi , by anterograde and retrograde tracing techniques. Quantitative image analysis was used to estimate the relative density and distribution of retinal input to different primary visual nuclei. The visual system of Spalax presents a mosaic of both regressive and progressive morphological features. Following intraocular injections of horseradish peroxidase conjugates, the retina was found to project bilaterally to all visual structures described as receiving retinal afferents in non‐fossorial rodents. Structures involved in form analysis and visually guided behaviors are reduced in size by more than 90%, receive a sparse retinal innervation, and are cytoarchitecturally poorly differentiated. The dorsal lateral geniculate nucleus, as defined by cyto‐ and myelo‐architecture, cytochrome oxidase, and acetylcholinesterase distribution as well as by afferent and efferent connections, consists of a narrow sheet 3–5 neurons thick, in the dorsal thalamus. Connections with visual cortex are topographically organized but multiple cortical injections result in widespread and overlapping distributions of geniculate neurons, thus indicating that the cortical map of visual space is imprecise. The superficial layers of the superior colliculus are collapsed to a single layer, and the diffuse ipsilateral distribution of retinal afferents also suggests a lack of precise retinotopic relations. In the pretectum, both the olivary pretectal nucleus and the nucleus of the optic tract could be identified as receiving ipsilateral and contralateral retinal projections. The ventral lateral geniculate nucleus is also bilaterally innervated, but distinct subdivisions of this nucleus or the intergeniculate leaflet could not be distinguished. The retina sends a sparse projection to the dorsal and lateral terminal nuclei of the accessory optic system. The medial terminal nucleus is not present. In contrast to the above, structures of the “non‐image forming” visual pathway involved in photoperiodic perception are well developed in Spalax . The suprachiasmatic nucleus receives a bilateral projection from the retina and the absolute size, cytoarchitecture, density, and distribution of retinal afferents in Spalax are comparable with those of other rodents. A relatively hypertrophied retinal projection is observed in the bed nucleus of the stria terminalis. Other regions which receive sparse visual input include the lateral and anterior hypothalamic areas, the retrochiasmatic region, the sub‐paraventricular zone, the paraventricular hypothalamic nucleus, the anteroventral and anterodorsal nuclei, the lateral habenula, the mediodorsal nucleus, and the basal telencephalon. These results indicate that the apparently global morphological regression of the visual system conceals a selective expansion of structures related to functions of photoperiodic perception and photo‐neuroendocrine regulation. We suggest that the evolution of an atrophied eye and reduced visual system is an adaptively advantageous response to the unique subterranean environment. Factors favoring regression include mechanical aspects, metabolic constraints, and competition between sensory systems. The primary advantage of sensory atrophy is the metabolic economy gained by the reduction of visual structures which do not contribute significantly to the animal's fitness. © 1993 Wiley‐Liss, Inc.

The classical "Bio Heat Transfer Equation (BHTE)" model is adapted to take into account the effects of oscillating microbubbles that occur naturally in the tissue during high-intensity focused ultrasound (HIFU) treatment. First, the Gilmore-Akulichev model is used to quantify the acoustic pressure scattered by microbubbles submitted to HIFU. Because this scattered pressure is not monochromatic, the concept of harmonic attenuation is introduced and a global attenuation coefficient is estimated for bubble-filled tissues. The first results show that this global attenuation coefficient varies significantly with respect to several parameters such as the frequency and the density of microbubbles in the medium, but also with respect to the incident acoustic pressure which thus becomes a transcendental function. Under these conditions, a layer-by-layer modeling, in the direction of propagation, is proposed to calculate the ultrasonic beam. Finally, the BHTE is solved and the HIFU-induced lesions are estimated by the calculation of the thermal dose. Using this model, it can be observed first that, when the firing power increases, the lesion develops clearly in the direction of the transducer, with a shape agreeing with in vivo experimentation. Next, it is observed that the lesion can be significantly modified in size and position, if an interface (skin or inner wall) is simulated as a zone with multiple cavitation nuclei. With a firing power increase, it is also shown how a secondary lesion can appear at the interface and how, beyond a certain threshold, this lesion develops at the main lesion expense. Finally, a better in-depth homogeneity of lesions is observed when the acoustic frequency of HIFU is increased.

PURPOSE OF REVIEW: The traditional focus of neurorehabilitaion has been on the patients' attention on their deficit, such that they should become aware of their problems and gain intentional control of compensatory strategies (descending approach). We review prism adaptation as one of the approaches that emphasize ascending rather than descending strategies to the rehabilitation of visuo-spatial disorders. The clinical outcome of prism adaptation highlights the need for a theoretical reconsideration of some previous stances to neurological rehabilitation. RECENT FINDINGS: Recent years have given rise to a growing body of experimental studies showing that the descending strategy is not always optimal, especially when higher-level cognition is affected by the patients' condition. Ascending approaches have, for example, used visuo-manual adaptation for the rehabilitation of visuo-spatial deficits. A simple task of pointing to visual targets while wearing prismatic goggles can produce remarkable improvements of various aspects of unilateral neglect. SUMMARY: The neural mechanisms underpinning visuo-manual plasticity can be viewed as a powerful rehabilitation tool that produces straightforward effects not only on visual and motor parameters, but on visuo-spatial, attentional and higher cognitive neurological functions. The use of prism adaptation therapy in neglect and other visuo-spatial disorders has just started to reveal its potential, both at a practical and theoretical level.

Using flow cytometry measurements combined with quantitative analysis of cell cycle kinetics, we show that rhesus monkey embryonic stem cells (ESCs) are characterized by an extremely rapid transit through the G1 phase, which accounts for 15% of the total cell cycle duration. Monkey ESCs exhibit a non-phasic expression of cyclin E, which is detected during all phases of the cell cycle, and do not growth-arrest in G1 after gamma-irradiation, reflecting the absence of a G1 checkpoint. Serum deprivation or pharmacological inhibition of mitogen-activated protein kinase kinase (MEK) did not result in any alteration in the cell cycle distribution, indicating that ESC growth does not rely on mitogenic signals transduced by the Ras/Raf/MEK pathway. Taken together, these data indicate that rhesus monkey ESCs, like their murine counterparts, exhibit unusual cell cycle features in which cell cycle control mechanisms operating during the G1 phase are reduced or absent.

The effect of epinephrine was tested on the proliferation of rat arterial smooth muscle cells (SMC) in secondary cultures. Epinephrine added daily to the culture medium caused a striking stimulation of growth. The effect increased with time and was dose-dependent. Maximal stimulation was observed at a concentration of 10(-5) M and after 72 hours. At higher concentrations (10(-3) M) epinephrine exhibited toxic effects on SMC. When SMC were maintained quiescent by deprivation of serum, the subsequent addition of epinephrine required serum to significantly enhance growth. This growth stimulation increased with serum concentration (from 0.1% to 10%). All the adrenergic agonists tested were found to stimulate SMC growth, with an activity classified by decreasing order as follows: norepinephrine greater than epinephrine greater than isoproterenol. Finally, this mitogenic response of SMC to catecholamines was specific since it could be blocked by adrenergic blocking agents, phentolamine being more efficient than propranolol in that connection. The results suggest that epinephrine and other catecholamines may act as growth factors for aortic SMC, at least in rat, mostly through adrenoreceptors.