Rem sleep without atonia--from cats to humans

Basic science research observations often lead to unexpected surprises. It is likely that in 1965 when Dr. Michel Jouvet placed bilateral peri-locus coeruleus lesions in cats and observed REM sleep without atonia (RWA) and "oneiric" behavior that could only be explained by "acting out dreams" (or "dreaming out acts"), he recognized that it was an important observation, but had little inkling of its true significance. Nor could he even imagine that it would lead to such greater understanding of wake/sleep phenomena in humans. Likely also, the first observation of REM sleep behavior disorder (RBD) in humans was felt to be interesting and novel - again with no true appreciation of what this seemingly simple observation would lead to important clinical relationships with numerous neurodegenerative disorders. The identification of RBD in humans also buttressed the concept of state dissociation, which has served to explain many previously unexplainable human behavioral phenomena.     

Effect of drugs of the nootropic class on rat behavior after deprivation of the paradoxical stage of sleep

Pharmacological analysis was used for studying the influence of 24-hour deprivation of paradoxical sleep by Jouvet method on retention of conditioned reaction of passive avoidance in rats. Psychotropic substances of different action were used for the analysis: nootropes as anti-amnestic--pyracetam (400 mg/kg), kleregil (100 mg/kg), centrofenoxin (50 mg/kg) and watersoluble salt of 3-oxypiridin derivative (3-OP) (50 mg/kg) and tranquilizer of bensodiazepine series phenazepam (1 mg/kg) as antistress and antiphobic. It was established that 24-hour deprivation disturbed the elaborated reaction but did not change the rate of emotionality and orienting-investigating behaviour of rats in the open field. Nootropes effectively restored the conditioned passive avoidance reaction while phenazepam had no effect. This allows to suggest that Jouvet method of paradoxical sleep deprivation elicits amnesia and its cause is not only stress but deficit of paradoxical sleep.     

Paradoxical (REM) sleep genesis: the switch from an aminergic-cholinergic to a GABAergic-glutamatergic hypothesis.

In the middle of the last century, Michel Jouvet discovered paradoxical sleep (PS), a sleep phase paradoxically characterized by cortical activation and rapid eye movements and a muscle atonia. Soon after, he showed that it was still present in "pontine cats" in which all structures rostral to the brainstem have been removed. Later on, it was demonstrated that the pontine peri-locus coeruleus alpha (peri-LCalpha in cats, corresponding to the sublaterodorsal nucleus, SLD, in rats) is responsible for PS onset. It was then proposed that the onset and maintenance of PS is due to a reciprocal inhibitory interaction between neurons presumably cholinergic specifically active during PS localized in this region and monoaminergic neurons. In the last decade, we have tested this hypothesis with our model of head-restrained rats and functional neuroanatomical studies. Our results confirmed that the SLD in rats contains the neurons responsible for the onset and maintenance of PS. They further indicate that (1) these neurons are non-cholinergic possibly glutamatergic neurons, (2) they directly project to the glycinergic premotoneurons localized in the medullary ventral gigantocellular reticular nucleus (GiV), (3) the main neurotransmitter responsible for their inhibition during waking (W) and slow wave sleep (SWS) is GABA rather than monoamines, (4) they are constantly and tonically excited by glutamate and (5) the GABAergic neurons responsible for their tonic inhibition during W and SWS are localized in the deep mesencephalic reticular nucleus (DPMe). We also showed that the tonic inhibition of locus coeruleus (LC) noradrenergic and dorsal raphe (DRN) serotonergic neurons during sleep is due to a tonic GABAergic inhibition by neurons localized in the dorsal paragigantocellular reticular nucleus (DPGi) and the ventrolateral periaqueductal gray (vlPAG). We propose that these GABAergic neurons also inhibit the GABAergic neurons of the DPMe at the onset and during PS and are therefore responsible for the onset and maintenance of PS.     

Paradoxical (REM) sleep genesis: The switch from an aminergic–cholinergic to a GABAergic–glutamatergic hypothesis

In the middle of the last century, Michel Jouvet discovered paradoxical sleep (PS), a sleep phase paradoxically characterized by cortical activation and rapid eye movements and a muscle atonia. Soon after, he showed that it was still present in “pontine cats” in which all structures rostral to the brainstem have been removed. Later on, it was demonstrated that the pontine peri-locus coeruleus α (peri-LCα in cats, corresponding to the sublaterodorsal nucleus, SLD, in rats) is responsible for PS onset. It was then proposed that the onset and maintenance of PS is due to a reciprocal inhibitory interaction between neurons presumably cholinergic specifically active during PS localized in this region and monoaminergic neurons. In the last decade, we have tested this hypothesis with our model of head-restrained rats and functional neuroanatomical studies. Our results confirmed that the SLD in rats contains the neurons responsible for the onset and maintenance of PS. They further indicate that (1) these neurons are non-cholinergic possibly glutamatergic neurons, (2) they directly project to the glycinergic premotoneurons localized in the medullary ventral gigantocellular reticular nucleus (GiV), (3) the main neurotransmitter responsible for their inhibition during waking (W) and slow wave sleep (SWS) is GABA rather than monoamines, (4) they are constantly and tonically excited by glutamate and (5) the GABAergic neurons responsible for their tonic inhibition during W and SWS are localized in the deep mesencephalic reticular nucleus (DPMe). We also showed that the tonic inhibition of locus coeruleus (LC) noradrenergic and dorsal raphe (DRN) serotonergic neurons during sleep is due to a tonic GABAergic inhibition by neurons localized in the dorsal paragigantocellular reticular nucleus (DPGi) and the ventrolateral periaqueductal gray (vlPAG). We propose that these GABAergic neurons also inhibit the GABAergic neurons of the DPMe at the onset and during PS and are therefore responsible for the onset and maintenance of PS.     

The influence of adrenergic and cholinergic blocking drugs on the glycogen content of the brain in rats deprived of paradoxical sleep

Recent studies have pointed out biochemical and pharmacological phenomena associated with the mechanism or mechanisms of sleep, especially in its paradoxical phase (Jouvet, 1964; Mandel, 1964). Our previous experiments have shown that paradoxical sleep (PS) deprivation leads to the fall of total glycogen content in certain regions of the brains of cats (Mr?ulja, Raki? and Radulova?ki, 1967; Mr?ulja and Raki?, 1968) and rats (Karad?i? and Mr?ulja, 1969). It was shown that changes of glycogen content correspond to PS deprivation and that PS deprivation is a specific stress to which the CNS responds selectively. Alterations in the glycogen concentration in a number of different brain structures lead us to conclude that neural areas affected by PS deprivation are widely distributed. Jouvet (1962) was one of the first to suggest that a neurohumoral mechanism may be concerned in the control of and characteristics of sleep. Experiments have shown that both cholinergic and adrenergic mechanisms may be involved in the initiation, maintenance and control of sleep. It has also been pointed out that paradoxical sleep can be started and maintained by cholinergic drugs (Matsuzaki, Okada and Shuto, 1967, 1968), blocked or reduced by anticholinergic compounds (Matsuzaki et al., 1968), and stimulated by noradrenaline or by its precursor, DOPA (Matsumoto and Jouvet, 1964). Bowers, Hartmann and Freedman (1966) showed that the ACh level of the rat telencephalon decreases with PS deprivation while the levels of norpinephrine and serotonin remain the same (Barchas and Freedman, 1963). More recently, Pujol, Mouret, Jouvet and Glowinski (1968) found the increased turnover of cerebral norepinephrine during rebound of PS in the rat. It is also of interest to point out that probably both adrenergic and cholinergic processes participate in the glycogenolytic effect of physostigmine (Mr?ulja, Terzi? and Varagi?, 1968). It was suggested that physostigmine initiates the cholinergic processes which then trigger off adrenergic processes. The aim in the present work was to determine the glycogen content in certain brain regions of rats which were subjected to PS deprivation lasting 72 hr and treated with some cholinergic or beta-adrenergic blocking agents, as well as with a catecholamine depleting drug.     

Beyond strain typing and molecular epidemiology: integrated genetic epidemiology of infectious diseases

In the past 20 years, genetic and molecular methods for characterizing pathogen strains have taken a major place in modern approaches to epidemiology of parasitic and other infectious diseases. Here, Michel Tibayrenc explains the main concepts used in this field of research, with special emphasis on the approaches developed in his team, and suggests future avenues to explore.     

Genes for prostaglandin d synthase and receptor as well as adenosine A2A receptor are involved in the homeostatic regulation of nrem sleep

(1) Prostaglandin D2 is essential for the maintenance of the sleep state. (2) The adenosine and A2A receptor system is a link between the humoral and neural mechanisms of sleep-wake regulation. (3) Prostaglandin D2 plays a crucial role in the homeostatic regulation of NREM sleep. Finally, it may not be too far-fetched to say that prostaglandin D2 was most likely the endogenous sleep substance described by Piéron and Ishimori about 100 years ago, and possibly the sleep-inducing factor reported by Professor Jouvet and coworkers some twenty years ago.     

Absorption of horse-radish peroxidase by the mucosal cells of the duodenum of mouse

Summary Horse-radish peroxidase was injected intraperitonealy to fasted and fed newborns. The protein was rapidly absorbed by the fasting animals and more slowly by the fed newborns. The tracer was progressively segregated into the supranuclear cluster of dense tubules and dense bodies. The cellular sap of several cells was deeply stained after the intraperitoneal injection. Control experiments showed that peroxidase has a high affinity for the matrix of the dense bodies in the first days of neonatal life.This work was supported by grants no. MA-3994 Medical Research Council of Canada, and by no. 9340-06 National Defense Board.The author is greatly indebted to Mr. Michel Couture for his skillful technical aid.     

Introduction to 'picturing eggs, embryos and cells'

Some twenty years ago, the historian of technology Henri Michel, who studied the history of instruments, wanted to draw our attention to the images des sciences (Michel 1977). Obviously, an instrument historian is well trained in dealing with pictorial matter, whether it may be blueprints of instruments, or detailed instructions about how to use and improve them. Further, instruments are extremely well suited media to demonstrate that theoretical knowledge has to be practically acquired, whether by making instruments, or by hand drawings. Also, historians of art have extensively worked, published and communicated on the issue of 'science and art' or 'science in art', and how their relationship shaped intellectual and technical history for several decades. As visualization denotes our ability to perceive, and to conceptualize, philosophy in general, and philosophy of science, in particular reflected about it and tried to grasp the scientists' epistemology. Over the last 25 years, an exceptional body of work was published on pictorial representation, either from a socio-cultural perspective, with an emphasis on the technology, or from the epistemic issue of how to conceptualize an eidon.     

From a civil engineering project to an ecological engineering project: An historical perspective from the Mont Saint Michel bay (France)

Because of an excess of sedimentation due to natural and anthropogenic causes, the Mont Saint Michel (France) is becoming less frequently surrounded by seawater during high tide events. This prestigious monument and its bay have both been recognized by multiple national and international institutions for cultural and ecological richness. Diverse human activities such as tourism, fisheries, and farming also occupy the Mont Saint Michel Bay. The French government has been faced with a challenge of preserving the integrity of the bay, while restoring the ‘insularity’ of what used to be an island, the Mont Saint Michel. The objective of this paper is primarily to demonstrate how environmental scientists and ecologists influenced a typical civil engineering project and modified it into a civil/ecological engineering project, more respectful of both environment and human interests. To achieve this objective, we first retrace the formation of the Mont Saint Michel Bay, under both geological and historical perspectives, to provide the necessary background for the understanding of the actual restoration project. Some of the first projects that were proposed were designed to destroy the area of salt marshes that surrounded the Mont Saint Michel, with no consideration for the ecological integrity of the site. We conclude by presenting the current project in which France will invest over 130 million USD in the next few years. If this final project cannot be recognized truly as an ecological engineering project, it has the merit of being a compromise between various partnerships which have been debating for more than a century.     

Malaria parasites: Randomly interbreeding or 'clonal' populations?

The 'clonality' hypothesis proposed by Michel Tibayrenc and his colleagues(1) has stimulated a long-overdue debate on the genetic structure of populations of protozoan parasites. A critical aspect of the hypothesis is the role of a sexual phase in the life cycle of these organisms. In the malaria parasite, Plasmodium, the existence of a sexual phase is unquestioned and is, indeed, a compulsory part of the cycle in the mosquito host. For this parasite, therefore, the principal question to be addressed, here by David Walliker, is whether populations of this parasite in nature are in a state of random mating (panmixia) or whether they comprise a limited number of clones which only occasionally undergo crossmating.     

The Policing of Race Mixing: The Place of Biopower within the History of Racisms

In this paper I investigate a largely untold chapter in the history of race thinking in Northern Europe and North America: the transition from the form of racism that was used to justify a race-based system of slavery to the medicalising racism which called for segregation, apartheid, eugenics, and, eventually, sterilization and the holocaust. In constructing this history I will employ the notion of biopower introduced by Michel Foucault. Foucault’s account of biopower has received a great deal of attention recently, but because what he actually has to say about race tends to be vague and radically incomplete, many race theorists have been critical of his contribution. However, even if the account of the holocaust in terms of biopower is incomplete, there is still a great deal to be learned from Foucault’s identification of this biologizing, or medicalising racism.     

Trainmasters or Easyjet pilots? Historical production,labor organizing,and the Spanish engine drivers’ union

This article presents an analysis of the relationship between historical memory and the emergence and reproduction of a specific model of unionism. I argue that in order to understand the militant particularism of the Spanish engine drivers, we need to look at the historical representations that it is embedded in. Recourse to a generational framework makes possible the sustained presentation of the union as a case of successful workers’ organizing, in spite of evidence to the contrary. The historical ethnographic analysis of SEMAF, the Spanish engine drivers’ union, contributes to the analysis of historical memory within the contemporary anthropology of class. The article contributes to theoretical debates in the anthropology of class by reclaiming Michel Trouillot’s conceptualization of the historical process. Two aspects of Trouillot’s work are singled out: his dynamic understanding of the process of historical production and the corollary formulation of the overlapping capacities in which people participate in it (as agents, actors, and subjects) and his emphasis on the importance of expanding scholarly views of the field of historical production.     

Diploid Ancestors of Triploid Export Banana Cultivars: Molecular Identification of 2<Emphasis Type="Italic">n</Emphasis> Restitution Gamete Donors and n Gamete Donors

The origin of triploid export banana cultivars was investigated. They all belong to Cavendish and Gros Michel subgroups of triploid clones and have a monospecific Musa acuminata origin. The appearance of these cultivars is thought to be result of hybridization between partially sterile diploid cultivars producing non reduced gametes and fertile diploids producing normal haploid gametes. To trace these diploid ancestors we compared the RFLP patterns, revealed by 36 probe/enzyme combinations, of 176 diploid clones representing the worldwide available variability with that of clones from the Cavendish and Gros Michel subgroups. This lead us to the identification of the common putative diploid ancestor of cultivars from Cavendish and Gros Michel subgroups which contributed to triploid cultivar formation through the production of 2n restitution gametes. For cultivars of Gros Michel subgroup we also propose a normal gamete donor that may have complemented the triploid allele set.     

Levels of plasma cholinesterase in Colombian working-class populations

Levels of plasma cholinesterase in Colombian working-class populations Reference values for plasma cholinesterase (EC 3.1.1.8) are not available for Colombian populations. A representative sample of a working-class population was used to establish these values to provide reference data for use by the social security system. Two working-class populations were sampled from the Aburrá Valley (Aburrá) and eastern Antioquia (Oriente). Cholinesterase activity was measured in 827 workers, with ages spanning 18-49 years, 415 from Aburrá and 412 people from Oriente. Three methods were used to measure cholinesterase: Michel, EQM and Monotest The average values by Michel and EQM were not statistically different between regions (Michel: Aburrá, 1.11, and East, 1.13 deltas pH/hora; EQM: Aburrá, 2.55, and Oriente, 2.48 U/ml). By the Monotest, the enzyme average was statistically higher in Aburra than in Oriente (5,743 and 5,459 U/L respectively; p = 0 .012). By region and technique, men had significantly higher enzymatic levels than women. Within both regions and sexes, no statistically significant difference among the three aged groups was noted. Our obtained Colombian values differed significantly from foreign reference values: Michel and Monotest levels were higher and EQM levels were lower. For making clinical and epidemiologic decisions in Colombia related to these data, the values obtained for the Colombian populations are preferred over values derived from external sources.     

Editor in Chief changes for Implementation Science

ABSTRACT: Implementation Science, like all journals, needs to continue to develop. There will always be changes we need to make as next steps in improving the Journal for readers and improving how it runs. However, we now have our first change in Editors in Chief. We are fortunate to have been able to recruit two experienced academics who are also experienced editors-- Professor Michel Wensing and Dr Anne Sales. I hope you will join me in welcoming them and give them, and continue to give Implementation Science, your support.     

Wieviorka's view on multiculturalism: a critique

Like any other society France is increasingly diversified culturally and in terms of collective identities. Clearly it is a multicultural, multi-identificational society, but it is not often willing to discuss openly the changes needed to accommodate its diversity and its de facto multicultural character. Michel Wieviorka has been courageous in trying to launch this crucial debate. In France his work is often appreciated but it is also often held to be ‘politically incorrect’ precisely because it questions the validity of the French republican model and its adequacy for the deep social changes at work in French society, and also because it raises the issue of the necessity of building a French multiculturalism. In this article the most important insights of Wieviorka's perspectives on multiculturalism are presented and some of the problems it implies are discussed.     

My Daily Constitutional in Martinsried

The three-dimensional structures of bacterial reaction centers have served as the framework for much of our understanding of anoxygenic photosynthesis. A key step in the determination of the structure of the reaction center from Rhodobacter sphaeroides was the use the molecular replacement technique. For this technique, we made use of two sets of data. First, X-ray diffraction data had been measured from crystals of the reaction center from R. sphaeroides by our research group in California, led by George Feher and Douglas Rees. The second data set consisted of the coordinates of the three-dimensional structure of the reaction center from Rhodopseudomonas (now Blastochloris) viridis, which had been solved in the pioneering efforts of a group in Martinsried, led by Johann Deisenhofer, Robert Huber and Hartmut Michel. The collaborative efforts of these two groups to determine the structure of the reaction center from R. sphaeroides is described.     

The prisoner as model organism: malaria research at Stateville Penitentiary

In a military-sponsored research project begun during the Second World War, inmates of the Stateville Penitentiary in Illinois were infected with malaria and treated with experimental drugs that sometimes had vicious side effects. They were made into reservoirs for the disease and they provided a food supply for the mosquito cultures. They acted as secretaries and technicians, recording data on one another, administering malarious mosquito bites and experimental drugs to one another, and helping decide who was admitted to the project and who became eligible for early parole as a result of his participation. Thus, the prisoners were not simply research subjects; they were deeply constitutive of the research project. Because a prisoner’s time on the project was counted as part of his sentence, and because serving on the project could shorten one’s sentence, the project must be seen as simultaneously serving the functions of research and punishment. Michel Foucault wrote about such ‘mixed mechanisms’ in his Discipline and punish. His shining example of such a ‘transparent’ and subtle style of punishment was the panopticon, Jeremy Bentham’s architectural invention of prison cellblocks arrayed around a central guard tower. Stateville prison was designed on Bentham’s model; Foucault featured it in his own discussion. This paper, then, explores the power relations in this highly idiosyncratic experimental system, in which the various roles of model organism, reagent, and technician are all occupied by sentient beings who move among them fluidly. This, I argue, created an environment in the Stateville hospital wing more panoptic than that in the cellblocks. Research and punishment were completely interpenetrating, and mutually reinforcing.     

Paradoxes, Problems, and Opportunities in Zaire

Zaire: The Cycle of the Serpent. 1992. 58 minutes, color. Directed by Thierry Michel. First Run/Icarus Films, 153 Waverly Place, New York, NY 10014. (212) 727-1711.
The Last Colonials. 1995. 61 minutes, color. Directed by Thierry Michel. First Run/Icarus Films, 153 Waverly Place, New York, NY 10014. (212) 727-1711.