Les percuteurs en pierre du site du Paléolithique moyen de Ketrosy,couche 3

The Middle Palaeolithic site Ketrosy (Middle Dniester valley) has been found and investigated by N.K. Anisyutkin in 1974–1979. He excavated 3 different complexes. The most interesting complex is the area № 1. It has the one (third) cultural layers in fair preservation, which had been dated appr. 100,000 years ago, by buried soils investigations. In the obtained collection, the hammerstones are represented by 19 pebbles with the traces of pecking. By its metrics, tools from Ketrosy fit within the framework of variability of the Middle – Upper Paleolithic hammerstones. But the location of the impact-marcs does not look ordinary and we suppose the transverse grip of the tools, conditioned, perhaps, by the anatomy of the inhabitants of the Ketrosy site. Low intensity of wear indicates “ad-hoc” mode of pebbles use as hammers. Spatial analysis of stone artifacts and bone remains (in particular – the context of hammers findings) confirm the short occupation and well-defined objects of cultural layer.     

Effets du GA3 et de la BAP sur la respiration,l’absorption et le métabolisme du phosphate chez des disques foliaires dePelargonium zonale après survie

Respiration rate of foliarPelargonium discs was insensitive to ageing. The addition of BAP or GA₃ to the ageing medium did not produce any effect. The presence of GA₃ or BAP in the ageing medium induced an increase (27 %) or a decrease (45 %) of the phosphate uptake. The analysis of phosphorylated compound labelling showed that these two hormones decreased³²P incorporation in the non-acid soluble fraction and increased³²P incorporation in the acid soluble organic fraction. GA₃ and BAP had little effect on the distribution of radioactivity between the different acid soluble compounds, but they increased the ATP level. These results suggest that both GA₃ and BAP increase the basal metabolism, but they seem to act differently on the development of the uptake mechanism during ageing.     

Traitement du cancer du testicule

Significant advances have been achieved in testicular cancer treatment for the last 15 years. Almost 100% of the non seminomatous tumors seen at the precocious stages I and II are cured because of the efficacy of chemotherapy in relapses. For clinical stages I, tendancy is to survey after castration without lymphadenectomy. For advanced metastatic stages, platinum has changed chemotherapy performances, allowing to cure 75 to 80% of these patients. The results of a bad pronosis group with large tumor remain to be improved. Seminomas at a localized stage (the most frequent case) are cured by radiotherapy; at an advanced stage, they are as sensitive to chemotherapy as non seminomatous tumors.     

Discontinuite hydrobiologique dans le detroit du Pas-de-Calais

Hydrobiological studies in the Straits of Dover show a differencebetween the characteristics of the French coastal water andthe open sea water. A cruise between Boulogne-sur-mer and Dover(October 15, 1985) confirms the existence of a frontal area(4 miles off the French coast). This area is characterized byan increase of the salinity (1%) and decrease of the suspendedmatter content (from 27 to 20 mg l^–1), of primary production(from 15 to 3 mg C m^–3h^–1) and of chlorophyll aconcentration (from 4.5 to 1.5 mg m^–3). The presence ofdifferent zooplanktonic species in the two water masses alsocharacterizes this discontinuity. Oncaea sp., Corycaeus anglicus,Centropages typicus and Calanus helgolandicus are indicatorspecies of open sea water, while Cyciopina littoralis and ‘Saphirella’are only present in coastal water.     

Analyse du débitage laminaire du site de Mezhyrich : habitations n 1, 2 et 3

This article presents the results of technological analyses of the laminar products from three bone dwelling structures from the Mezhyrich site (dated to Upper Palaeolithic; 15,000–14,500 years BP). More than 2500 blades and bladelets were studied from technological point of view. We find close similarity between the three dwellings, which reflects similar ways of preparation of core fracture zone (overhang reduction, butt abrading, and flaking surface isolation), as well as in the organization of the negative of the dorsal surfaces of the blades. The comparison with materials from the Kostenki 1 layer 1 site (upper layer, 22,000–24,000 years BP) shows some differences with the artefacts from Mezhyrich site, despite same technological methods. This could be explained by differences in cultural tradition and large time gap between these two sites. The complexes from Mezhyrich to follow the Kostenki 1/1 tradition but with their own particularities.     

Analyse du statut oxydatif spermatique chez des patients infertiles

Introduction

Male infertility constitutes public health problems. Several factors are at the origin of this phenomenon. Currently, the oxidative stress is accused to be one of the leading causes. In our study, we sought a correlation between the markers of the oxidative stress and the sperm characteristics (morphology).

Material and methods

We evaluated the antioxidant status in the seminal plasma of 129 infertile men. Patients were characterized by infertility of variable duration. They were divided into four groups: normozoospermics who were considered as controls (n=34), asthenozoospermics (Astheno; n=43), oligozoospermics (Oligo; n=22) and teratozoospermics (Terato; n=30). Among the oxidative stress markers, we evaluated, in seminal plasma, zinc, calcium, magnesium and selenium by spectrophotometry of atomic absorption to flame and furnace. The malondialdehyde (MDA) is proportioned by spectrofluorometry.

Results

Our results show that the seminal concentrations of zinc and selenium are higher in the control group than the concentrations of these same elements in the three other groups. The seminal zinc concentration was significantly correlated with the sperm count (r=0.49; p < 0.001) and MDA (r=- 0.35; p<0.05). Sperm motility was correlated with calcium (r=0.41; p<0.001) and magnesium (r=0.31; p<0.05). The MDA concentration is higher in the three groups of patients: oligozoospermics (3.22±1.37 ??g/ml), asthenozoospermics (3.52±1.93 ??g/ml) and teratozoospermics (3.64±1.73 ??g/ml) compared with controls (2.32±0.94 ??g/ml). A single positive correlation was observed between the MDA and morphology (r=0.19; p<0.05).

Conclusion

Our study confirms that the oxidative stress plays an important role in the process of deteriorations of the spermatozoa. The free radicals can, indeed, modify the membrane structure as well as the membrane structure of the deoxyribonucleic acid. These deteriorations also lead to an increase in the percentage of sperm of abnormal forms.     

Les brisures de symetrie du temps

Introduction

Atoms theory and symmetry theory dominated physics. Symmetry propagation and interactions verify the Curie principle. But its violation by symmetry breaking is spontaneous.Fragility is creative. An information breaks a generalized symmetry. Results on symmetry breakings are not valid for fuzzy symmetries. The breaking of a fuzzy symmetry leads only to a pour symmetry (Fig.1). Homogeneity breaking, and atom of time are not usual concepts. We examine in this work symmetry breakings which generate the living time.

Relativistic Time-Space Breaking

1. Medium and environment of living define ordinary referential of space and referential of time. Astronomical phenomena following classical mechanics and microphysical phenomena following quantum mechanics can be written with the same t coordinate.
2. Relativity corrections. Schrödinger's Quantum mechanics (Eq.0) approximately governs molecular systems (Relativity corrections can be expressed as physical effects in the above defined referential).
3. Time reversal symmetry. The well-known Wigner's transformation determines the microscopic reversibility.
4. The three essential particle-vacancy equilibria. This transformation is verified by all particle-vacancy reciprocity. Vacancy moves like particle but with negative moment and positive kinetic energies. Only three biochemical equilibria admit this time reversal symmetry, namely: oxydo-reduction, acido-basicity, fluidity-viscosity. In these case, reacting electron, solvated proton, water molecule are respectively antagonist of the corresponding vacancy.
5. Fuzzy character of time reversal symmetry. Dirac's equation does not admit this symmetry which only appears at the “non relativistic” limit of quantum phenomena. Hence particle-vacancy reciprocity is fuzzy according to the experimental evidence. (Laforgue et al., 1988).

Oriented Time

1. From the universal reversible time, an additional breaking generates the oriented time, both in the astronomical and in the living matter.
2. Irreversibility for the environment. We refer to Prigogine and Stengers (1988).
3. Irreversibility for the living matter. We refer to Lochak (1986). Because equation (0), above discussed, is “microreversible” the second breaking could come from an additional term vanishing in the stationary states but increasing with time in evolutionary processes.
4. Negative times. Taking into account the fuzzy character of the time reversal symmetry, the third breaking cannot suppress completely the occurrence of negative times. Reversed time is controlled by direct time. Except in the three above reported cases, time reversal symmetry is not verified by the medium. Free motion of the particle following eg.(0) or of the vacancy following time reversal reciprocal equation takes place only during short jumps from an interaction site to an other. Fig. 2 schematizes the law of motion of the electric charge corresponding to the transport by proton or by proton vacancy in an unitary field (fluctuations are neglected). The reserved jumps are estimated in the range of 10^?12s. It is not excluded that such a jump can control a direct phenomenon.
5. The living time. Biological phenomenon appears as an oriented set of events. Nevertheless latency or exaltation phases could be perceived. This modulation could be described by positive and negative times additional to the basic time. (Negative can be interpreted as above.)

Living produces Time

1. That were not understandable, if time was only a frame, in which change occurs. Taking change as frame and time as effect, we regard biological activity as integrating reversible and irreversible time. Living synchronizes internal and external time by its own effort as it results (Lestienne, 1990) from Chronobiology.
2. Time modulation. Let us consider the dy₁...dy_i...dy_p changes in the variables of the system, dy={dy_i} has produced dt. We proof (eq.(1) to (4)) that time is modulated by a Φ_(y) speed coefficient depending on the medium. t_modulated=tΦ^-1 _(y)
3. The production of reversible time (e.g.acido-basicity) determines time modulation. As above reported it remains some reversibility effects (jumps of negative time) which modulate time. E.g., if an important amount of reagent is necessary to modify an acid-base equilibrium, Φ_(y) is small.
4. Time modulation and activation-repression reciprocity. As well-known, long t_modulated means repression, short t_modulated means exaltation. Extrema of ? are symmetrical because particle and vacancy are reciprocal. Nevertheless reciprocity is not perfect. E.g., on fig. 3, the wet receptor determines the cell increasing, the dry receptor the cell senescence of a certain alga (Lück, 1962).
5. Irreversible time production. Medium accepts entropy. Hence it acts in the second breaking of time. Living extracts the free energy from the medium, like a dissipative structure. That insures an operative point far from the thermodynamical equilibrium.

Consumption of Time

1. The three followings correspond to the more trivial time consumption.
2. Rhythmical time. Free energy flux is favourable to the arising of order in space or time. This later gives a structure to the living time.
3. Mutual dependence of reversible time and rhythms. Time irreversible structure can be controlled by the above considered particle-vacancy equilibrium. Consequently the living time (modulated and structured) is a chemical time connected to molecular properties and to statistical thermodynamics. Practically, the connection between chronobiology and chemistry is important. The use of drugs could be interpreted as a response to an aggression against biorhythms.
4. Lifetime. The dead-birth rhythm can be broken in two ways: evolution or indefinite life. This later is non exceptional for the living matter, e.g. in the vegetals where it is connected with the chlorophyllic assimilation; the time reversal significance of which is evident.
5. The plan of the alchemist. Indefinitely life has fascinated individuals. Do the human species becomes better adapted by a longer life?

Conclusions

1. Atoms of time could exist.
2. Biological time is defined by the breaking of five generalized symmetries, namely: Minkovski's space symmetry, reversibility, homogeneity, rhythmicity, generations reproduction.
3. Environment and medium determine non relativistic, oriented, structured time.
4. At the microphysical scale, a fuzzy time reversal symmetry takes place, the breaking of which is not complete. Reversible time and dominating irreversible time are integrated in living phenomena.
5. Three fundamental particle-vacancy reciprocities admit a part of reversibility. Irreversibility governs the all others phenomena.
6. Time is produced chemically.
7. A new perspective is the connection between chemical equilibria and rhythms including the time of the life.

     

Les hommes de Néandertal du Caucase du Nord : entre l’Ouest et l’Est

A geographical position of the Caucasus in the border between Europe and Asia defines a complex character of the Middle Paleolithic in the region as a whole and in the Northern Caucasus in particular. Today, we can recognize three major cultural areas existed during the Middle Paleolithic in the Northern Caucasus: (1) a local North Caucasian variant of Eastern Micoquian, which is closely related to Eastern Micoquian of Central and Eastern Europe, in the Northwestern Caucasus; (2) a specific Caucasian industry type (called Khostinian Mousterian), which penetrated during later MIS 3 to the Northwestern Caucasus from the Northeastern Black sea cost in the Southern Caucasus; and (3) a similar to Zagros Mousterian industry, which is presented in Weasel Cave in the Northeastern Caucasus.     

Transfert du galactose dans les membranes des globules lipidiques du lait humain

Galactose transfer in the membranes of human milk fat globulesGalactosyltransferase which catalyzes the transfer from UDP-galactose to either endogeneous glycoproteins, free N-actylglucosamine or N-acetylglucosaminyl residues in the carbohydrate portion of glycoproteins, or to glucose when α-lactalbumin is added, occurs in human milk fat globule membranes. Various treatments (washing of membranes, freezing and thawing) did not affect this activity. In the presence of Triton X-100, the enzyme shows appreciable latency. This detergent was then used to solubilize the enzyme and to study its main characteristics. A competition and a heat stability experiment show that only one enzyme acts on two substrates (free N-acetylglucosamine or desialyzed and degalactosylated fetuin). UDP-galactose hydrolase activities were very low compared to those of the bovine milk fat globule membranes. Other characteristic enzymes of Golgi vesicles were found in human milk fat globules membranes. It is of interest to find out whether this is the result of contamination with cytoplasmic particles or whether it reflects the participation of Golgi vesicles in human milk fat globule secretion.     

Les brisures de symetrie du temps

Introduction

Atoms theory and symmetry theory dominated physics. Symmetry propagation and interactions verify the Curie principle. But its violation by symmetry breaking is spontaneous.Fragility is creative. An information breaks a generalized symmetry. Results on symmetry breakings are not valid for fuzzy symmetries. The breaking of a fuzzy symmetry leads only to a pour symmetry (Fig.1). Homogeneity breaking, and atom of time are not usual concepts. We examine in this work symmetry breakings which generate the living time.

Relativistic Time-Space Breaking

1. Medium and environment of living define ordinary referential of space and referential of time. Astronomical phenomena following classical mechanics and microphysical phenomena following quantum mechanics can be written with the same t coordinate.
2. Relativity corrections. Schrödinger's Quantum mechanics (Eq.0) approximately governs molecular systems (Relativity corrections can be expressed as physical effects in the above defined referential).
3. Time reversal symmetry. The well-known Wigner's transformation determines the microscopic reversibility.
4. The three essential particle-vacancy equilibria. This transformation is verified by all particle-vacancy reciprocity. Vacancy moves like particle but with negative moment and positive kinetic energies. Only three biochemical equilibria admit this time reversal symmetry, namely: oxydo-reduction, acido-basicity, fluidity-viscosity. In these case, reacting electron, solvated proton, water molecule are respectively antagonist of the corresponding vacancy.
5. Fuzzy character of time reversal symmetry. Dirac's equation does not admit this symmetry which only appears at the “non relativistic” limit of quantum phenomena. Hence particle-vacancy reciprocity is fuzzy according to the experimental evidence. (Laforgue et al., 1988).

Oriented Time

1. From the universal reversible time, an additional breaking generates the oriented time, both in the astronomical and in the living matter.
2. Irreversibility for the environment. We refer to Prigogine and Stengers (1988).
3. Irreversibility for the living matter. We refer to Lochak (1986). Because equation (0), above discussed, is “microreversible” the second breaking could come from an additional term vanishing in the stationary states but increasing with time in evolutionary processes.
4. Negative times. Taking into account the fuzzy character of the time reversed symmetry, the third breaking cannot suppress completely the occurrence of negative times. Reversed time is controlled by direct time. Except in the three above reported cases, time reversal symmetry is not verified by the medium. Free motion of the particle following eg.(0) or of the vacancy following time reversal reciprocal equation takes place only during short jumps from an interaction site to an other. Fig. 2 schematizes the law of motion of the electric charge corresponding to the transport by proton or by proton vacancy in an unitary field (fluctuations are neglected). The reserved jumps are estimated in the range of 10^?12s. It is not excluded that such a jump can control a direct phenomenon.
5. The living time. Biological phenomenon appears as an oriented set of events. Nevertheless latency or exaltation phases could be perceived. This modulation could be described by positive and negative times additional to the basic time. (Negative can be interpreted as above)

Living produces Time

1. That were not understandable, if time was only a frame, in which change occurs. Taking chance as frame and time as effect, we regard biological activity as integrating reversible and irreversible time. Living synchronizes internal and external time by its own effort as it results (Lestienne, 1990) from Chronobiology.
2. Time modulation. Let us consider the dy₁...dy_i...dy_p changes in the variables of the systems, dy={dy_i} has produced dt. We proof (eq.(1) to (4)) that time is modulated by a φ_(y) speed coefficient depending on the medium. t_modulated=tφ _(y) ^?1
3. The production of reversible time (e.g.acido-basicity) determines time modulation. As above reported it remains some reversibility effects (jumps of negative time) which modulate time. E.G., if an important amount of reagent is necessary to modify an acid-base equilibrium, φ_(y) is small.
4. Time modulation and activation-repression reciprocity. As well-known, long t_modulated means repression, short t_modulated means exaltation. Extrema of ? are symmetrical because particle and vacancy are reciprocal. Nevertheless reciprocity is not perfect. E.g., on fig. 3, the wet receptor determines the cell increasing, the dry receptor the cell senescence of a certain alga (Lück, 1962).
5. Irreversible time production. Medium accepts entropy. Hence it acts in the second breaking of time. Living extracts the free energy from the medium, like a dissipative structure. That insures an operative point far from the thermodynamical equilibrium.

Consumption of Time

1. The three followings correspond to the more trivial time consumption.
2. Rhythmical time. Free energy flux is favourable to the arising of order in space or time. This later gives a structure to the living time.
3. Mutual dependence of reversible time and rhythms. Time irreversible structure can be controlled by the above considered particle-vacancy equilibrium. Consequently the living time (modulated and structured) is a chemical time connected to molecular properties and to statistical thermodynamics. Practically, the connection between chronobiology and chemistry is important. The use of drugs could be interpreted as a response to an aggression against biorhythms.
4. Lifetime. The dead-birth rythm can be broken in two ways: evolution or indefinite life. This later is non exceptional for the living matter, e.g. in the vegetals where it is connected with the chlorophyllic assimilation; the time reversal significance of which is evident.
5. The plan of the alchemist. Indefinitely life has fascinated individuals. Do the human species becomes better adapted by a longer life?

Conclusions

1. Atoms of time could exist.
2. Biological time is defined by the breaking of five generalized symmetries, namely: Minkovski's space symmetry, reversibility, homogeneity, rhythmicity, generations reproduction.
3. Environment and medium determine non relativistic, oriented, structured time.
4. At the microphysical scale, a fuzzy time reversal symmetry takes place, the breaking of which is not complete. Reversible time and dominating irreversible time are integrated in living phenomena.
5. Three fundamental particle-vacancy reciprocities admit a part of reversibity. Irreversibility governs the all others phenomena.
6. Time is produced chemically.
7. A new perspective is the connection between chemical equilibria and rhythms including the time of the life.

     

Presence du Messinien dans la vallee du Rhone

According to the paleontological (molluscs and ostracods) and stratigraphical data, the Congeria rhodanicacclays are of Upper Messinian age. This oligohaline facies points out the local transgression of mediterranean origin in the Rhone basin, following a Lower Messinian erosive episode with coarse subaerial partial valley infill.     

Histochimie des mono-amine-oxydases du tronc cerebral du rat: noyaux latero-dorsal du tegmentum et interpedonculaire

Résumé L'étude histochimique des Mono-Amine-Oxydases (MAO) des noyaux gris du tronc cérébral: interpédonculaire et latéro-dorsal du tegmentum a été réalisée chez 30 rats albinos mâles et femelles.La méthode de Glenner avec les sels de Tétrazolium, modifiée par Shimizu, a été employée et nous a permis de confirmer les travaux de ces auteurs et ceux de Smith.Le noyau latéro-dorsal du tegmentum paraît avoir la plus forte teneur en MAO du cerveau; sa coloration est dense, homogène, diffusant légèrement autour du site observé lors de l'étude histologique par la méthode d'Einarson à la Gallocyanine.Au contraire, celle du noyau interpédonculaire est moins intense, non homogène, plus marquée latéralement.L'action in vivo des inhibiteurs spécifiques des MAO (Phénelzine, Nialamide) confirme la disparité de ces deux noyaux: la dose minimale efficace pour inhiber totalement les MAO du n. interpédonculaire est insuffisante pour le n. latéro-dorsal du tegmentum.La Phénelzine a une action beaucoup plus précoce et plus complète que le Nialamide; leurs durées d'action sont voisines.

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Summary The histochemical study of the Mono-amine-oxidases (MAO) in the nuclei interpeduncularis and latero-dorsalis tegmenti of the brain stem was made over 30 male and female albinos rats.The Glenner's method with Tetrazolium salts, modified by Shimizu, was used and enabled us to confirm the works of these authors and Smith as well.The coloration of the nucleus latero-dorsalis tegmenti is of a strong and homogeneous density and spreading slightly all around the spot observed during the histological study with Gallocyanin after Einarson's method.On the contrary, the coloration of the nucleus interpeduncularis is less strong, without any homogeneity, and of thicker density on the edges.The activity in vivo of the specific inhibitors of MAO (Phenelzin, Nialamid) confirms the disparity of their 2 nuclei. Phenelzin operates earlier and more completely than Nialamid. The time of their action is similar.

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Remerciements. Nous remercions Meile Gontcharoff (lab. Biologie Générale) et Mr Jacquot (lab. Physiologie Animale) de la faculté des Sciences de Reims, qui nous ont acceuilli généreusement dans leur laboratoire et nous ont permis de réaliser cette étude. Nous exprimons notre gratitude envers Mr Jouvet (lab. Médecine expérimentale, faculté de Médecine, Lyon) qui nous a adressé ses critiques.Nos remerciements vont aussi à Mr Lechenault, Maître-Assistant de Biologie Générale (Fac. des Sciences, Reims) qui nous a prodigué ses conseils compétents et sans qui cette étude n'aurait pu être menée à bien.     

Identification de metabolites du dimethyl-1,3-(benzothiazolyl-2)-3-uree et etude de sa stabilite in vitro

Structures of some metabolites of methbenzthiazuron (MBT) obtained by hydroponic culture in different plants have been elucidated. It is possible to isolate 1-hydroxymethyl-3-methyl-3-(2-benzothiazolyl)-urea, representing the first step in urea chain degradation. The loss of the hydroxymethyl group gives a second metabolise. Condensation with glucose represents another way of physiological neutralisation. The synthesis of other possible derivatives of MBT has failed to indicate the nature of other metabolites that are formed in uivo. The reaction of MBT to UV light has also been examined.     

Incidence du cancer du testicule au niveau mondial

Testicular cancer (TC) is the commonest malignancy in men aged 20 to 34 years. We reviewed the statistical sources of the IARC, and summarized the published studies on the increasing incidence rates of TC in the world. We observed a variation of incidence rates according to the geographical situation. The majority of industrialized countries, North-America, Europe, and Oceania showed higher incidence rates than Asian or African countries. Nevertheless, surprising differences in TC incidence rates were observed between neighboring countries and also between different regions in the same country. Substantial differences in TC incidence were also observed between ethnic groups. A clear trend towards an increase in TC incidence over the last decades was revealed. The increase in TC incidence was associated with a strong birth cohort effect in the USA, and also in European countries. Previous studies have not been able to explain the variation of worldwide incidence rates and its increase. Although male reproductive abnormalities assumed to be related to exposure to high levels of endogenous oestrogens during pregnancy, further studies are required before any conclusions can be drawn.     

L'evolution postembryonnaire du poids du pigeon domestique

Summary A detailed study of the postembryonic evolution of the weight of the pigeon, by means of daily weighing of the young birds, is given (table). The young bird grows very fast during the first days of its postembryonic life, the classical S shaped growth curve being steep in the beginning. Growth slows down during the period the feeding changes from crop milk to grains regurgitated from the crop of the parents, and also during the period that the young bird begins to come out of the nest and to feed on his own (Fig. 1).The rate of growth is affected by the quantity of food the young bird receives: in normal conditions there are two young for a couple of parents; when there is only one young, it grows faster; the differences are significative till the 16^th day of age (table).     

Mot du rédacteur en chef

BACKGROUND: As the interval between rupture of the fetal membranes at term and delivery increases, so may the risk of fetal and maternal infection. Recently the TERMPROM (Term Prelabor Rupture of the Membranes) Study Group reported the results of a randomized controlled trial comparing 4 management strategies: induction with oxytocin (IwO), induction with prostaglandin (IwP), and expectant management and induction with either oxytocin (EM-O) or prostaglandin (EM-P) if complications developed. The study found no statistically significant differences in neonatal infection and cesarean section rates between any of the 4 groups. OBJECTIVE: To conduct an economic evaluation comparing the cost of (a) IwO and EM-O, (b) IwP and EM-P and (c) IwO and IwP. DESIGN: An economic analysis, conducted alongside the clinical trial, using a third-party payer perspective. Analysis included all treatment costs incurred for both the mother and the baby. Information on health care utilization and outcomes was collected for all study participants. Three countries (Canada, the United Kingdom and Australia), corresponding to the largest study recruitment, were chosen for calculation of unit costs. For each country, the base, low and high estimates of unit cost for each service item were generated. Intention-to-treat analysis. Extensive statistical and sensitivity analyses were performed. RESULTS: The median cost of IwO per patient was significantly lower statistically than that of EM-O and IwP. This result held in all 3 countries compared -$114 and -$46 in Canada, -113 Pounds and -63 Pounds in the UK, and -A$30 and -A$49 in Australia) and after an extensive sensitivity analysis. There was no statistically significant difference in median cost per patient between IwP and EM-P. CONCLUSION: Although the clinical results of the TERMPROM study did not find IwO to be preferable to the other treatment alternatives, the economic evaluation found it to be less costly. However, these cost differences, even though statistically significant, are not likely to be important in many countries. When this is the case, the authors recommend that women be offered a choice between management strategies.     

The Cirque du Soleil of Golgi membrane dynamics

The role of lipid metabolic enzymes in Golgi membrane remodeling is a subject of intense interest. Now, in this issue, Schmidt and Brown (2009. J. Cell Biol. doi:10.1083/jcb.200904147) report that lysophosphatidic acid–specific acyltransferase, LPAAT3, contributes to Golgi membrane dynamics by suppressing tubule formation.The idea that active remodeling of glycerolipid acyl chains contributes to the membrane transformations required for membrane trafficking is not new (Kozlov et al., 1989; Chernomordik et al., 1995). However, identification of specific enzymes that execute such functions in living cells has proven elusive. Now, an interesting study by Schmidt and Brown (see p. 211 of this issue) demonstrates that a lysophosphatidic acid acyltransferase (LPAAT) is directly involved in regulating mammalian Golgi trafficking functions. A variety of experimental approaches converge on a coherent model where LPAAT3 quenches the formation of Golgi-derived tubules. In doing so, LPAAT3 opposes what is most likely a phospholipase A₂–mediated tubulation pathway. This balance of PLA₂ and LPAAT3 activities has functional consequences for membrane trafficking from the mammalian Golgi complex.Glycerolipids, such as phosphatidic acid (PtdOH), consist of a glycerol backbone to which three additional constituents are esterified. Fatty acyl chains are attached at the sn-1 and sn-2 positions, and these lend glycerolipids their hydrophobic character. The headgroup at the sn-3 position can be very simple (an −OH group to generate diacylglycerol; DAG) or complex (i.e., another glycerolipid molecule). In the case of phospholipids, the headgroup is linked to the backbone by a phosphoester bond (PtdOH representing the simplest case). The three-dimensional shape of a phospholipid molecule (cone, inverted cone, cylinder) is governed by the ratio of the axial area of the headgroup to that of the acyl chain region. Because the sn-2 acyl chain is often unsaturated, and therefore kinked, a suitably bulky headgroup is required to match the axial area of the acyl chain region and generate a cylindrical molecule that packs into orderly membrane bilayers. The basic principle is lipid shape can be regulated at the level of either the headgroup or the acyl chains, and enrichment of non-cylindrical lipid molecules will physically deform membranes in predictable ways (Burger, 2000; Kooijman et al., 2005).Phospholipase A₂ (PLA₂) hydrolyzes the acyl chain from the sn-2 position of a glycerolipid molecule and, in doing so, generates a molecule with a glycerol backbone esterified to a fatty acid at sn-1 and to the headgroup at sn-3. This lyso-lipid exhibits a small axial area for the acyl chain region (and is shaped as an inverted cone that promotes positive membrane curvature). What LPAATs do is re-acylate the sn-2 position with a second fatty acid (or more accurately, a fatty acyl-CoA with release of CoA as product), often an unsaturated one in higher eukaryotes, so that the axial area of the acyl chain region is much increased. When the headgroup of the glycerolipid is small, as is the case with PtdOH and DAG, the renovated glycerolipid molecule now assumes a cone shape that promotes negative membrane curvature. The general deacylation/reacylation cycle driven by sequential PLA₂/LPAAT actions of this sort is termed the Lands cycle (Fig. 1; Lands and Hart, 1965). Although originally discovered as a metabolic pathway for phospholipid acyl chain remodeling in liver, the Lands cycle now resurfaces as a mechanism for controlling mammalian Golgi membrane dynamics.Open in a separate windowFigure 1.The Lands cycle. PLA₂ hydrolyzes the acyl-chain from a glycerophospholipid to generate a free fatty acid and a lysophospholipid product. Reacylation of lysophospholipid back to a glycerophospholipid (often with a different acyl chain at sn-2) is catalyzed by an LPAAT and involves consumption of a fatty acyl-CoA. This figure was adapted from Figure 5 in Shimizu (2009).LPAATs have been studied previously from the perspective of the enzymology of lipid metabolism, but their functions from the cell biological point of view remain poorly understood. The human genome sequence database identifies nine potential LPAATs (Leung, 2001; Shindou and Shimizu, 2009). A functional involvement of the Lands cycle (and LPAATs) with the Golgi complex was initially forecast by pharmacological studies with PLA₂ and LPAAT inhibitors—the former insults interfering with various membrane trafficking pathways and the latter promoting others (de Figueiredo et al., 1998, 2000; Drecktrah et al., 2003; Chambers et al., 2005). Unfortunately, inhibitor studies of this sort are difficult to interpret. For instance, do the pleiotropic effects of the drugs report inhibition of multiple enzyme isoforms with various execution points, or are these reflections of “off-target” effects?Schmidt and Brown (2009) now report the integral membrane protein LPAAT3 localizes to ER/Golgi membranes and exhibits lyso-PtdOH acyltransferase activity. Modulation of LPAAT3 expression has significant consequences for Golgi organization and function. siRNA-mediated silencing of LPAAT3 expression resulted in Golgi fragmentation into mini-stacks, an exquisite sensitivity of Golgi integrity to brefeldin A (BFA), and elevated mis-localization of Golgi resident proteins to the ER. Reciprocally, elevated LPAAT3 expression retards Golgi collapse into the ER upon BFA challenge. These various effects correlate with enhanced formation of Golgi-derived tubules in the face of LPAAT3 inhibitors (lyso-PtdOH formation favored) and depressed tubule biogenesis when LPAAT3 activity is increased (conversion of lyso-PtdOH to PtdOH favored). Tubulation is clearly relevant to membrane transport, as enhancement can (in specific cases) accelerate rates of cargo trafficking. Interference with tubule biogenesis, or maintenance, retards trafficking from the Golgi complex, and both anterograde and retrograde trafficking pathways are affected (Schmidt and Brown, 2009).The simple physical principle that connects the Lands cycle to tubulation is that production of inverted cone lyso-PtdOH by a PLA₂ strongly promotes positive membrane curvature and tubulation, whereas LPAAT3-mediated reacylation of lyso-PtdOH to PtdOH has the opposite effect (Fig. 2). Curvature parameters have been measured for lyso-PtdOH and PtdOH at physiological salt and pH concentrations, and the respective spontaneous radii of curvatures are +20Å and −46Å, respectively (for oleoyl molecular species; Kooijman et al., 2005). Interestingly, the measurements for lyso-PtdOH yield among the highest positive curvature values recorded to date. One testable question for future investigation is whether the PtdOH molecular species generated in Golgi membranes by LPAAT3 differ from those of bulk Golgi membrane PtdOH; that is, whether reacylation generates PtdOH molecular species with distinct properties such as unsaturated acyl chains at sn-2. Such a result would forecast an acyl-chain preference for LPAAT3 and the resultant molecular species would assume more extreme cone shapes that may contribute to the membrane transformations that accompany fission processes (Burger, 2000; Kooijman et al., 2005). It is also possible that newly remodeled PtdOH is a precursor for DAG, which may be the operative fission-ogenic glycerolipid. DAG assumes even more extreme negative curvatures than does PtdOH, and it is not subject to electrostatic penalties associated with packing the highly negatively charged PtdOH headgroup. Critical roles for DAG in Golgi membrane trafficking are well established (Kearns et al., 1997; Baron and Malhotra, 2002; Fernandez-Ulibarri et al., 2007; Asp et al., 2009).Open in a separate windowFigure 2.Protein domains consolidate the positive membrane curvature generated by lyso-PtdOH. PLA₂ hydrolyzes the acyl-chain from a phosphatidylcholine (PtdCho: cylindrical lipid) to generate a free fatty acid (FFA) and a lyso-PtdCho product (positive curvature). That lyso-PtdCho (LPC) species is further metabolized to lyso-PtdOH (LPA; greater positive curvature) by phospholipases with concomitant release of the choline (Cho) headgroup. The LPA is bound by proteins that “sense” curvature or bend membranes (e.g., BAR domain), leading to further sorting of LPA to the site of deformation (in this case a budding profile). LPAAT3 antagonizes this pathway by consuming lyso-PtdOH into PtdOH synthesis. The figure was adapted from one generously provided to V.A. Bankaitis by Wonhwa Cho (University of Illinois-Chicago, Chicago, IL).How may proteins interface with the Lands cycle in the Golgi system? Do proteins provide the primary driving force for membrane deformation, or is lipid metabolism the major factor? It is unlikely to be solely the latter—at least in this case. Simple activity of PLA₂ in generating lyso-PtdOH (or other lyso-lipids) is insufficient to impose significant positive curvature to membranes. The liberated fatty acid product will promote negative curvature—thereby countering the effects of the lyso-lipid. Enrichment of lyso-lipid into domains is a prerequisite for membrane deformation, and such enrichment can be reinforced by proteins in several ways. First, protein domains that bend membranes (e.g., BAR-domains; Frost et al., 2009) could bind lyso-lipids by virtue of their shape characteristics and thereby consolidate them into positively curved domains (Fig. 2). Second, coat or motor proteins that mechanically generate tubules could drive a physical rearrangement of membrane lipids to structures that best fit their shape (Roux et al., 2005; Krauss et al., 2008; Sorre et al., 2009). In this scenario, lyso-lipids re-sort preferentially to tubules and generate a positive feedback loop for membrane deformations with positive curvature.Reconstituted systems for membrane deformation use metabolically inert membranes, and are deprived of the active interface between lipid metabolism, proteins, and membrane dynamics. What blind spots are inherent in such protein-driven membrane deformation assays remains to be seen, but it will prove increasingly true that diverse pathways of lipid metabolism, including the Lands cycle, lubricate the actions of proteins in productive membrane deformation pathways. Which is more important—proteins or lipids—in this arena? Let’s call it an equal-opportunity collaboration.Given the intense interest concerning interfaces of lipid metabolism and Golgi function, it is difficult to believe that the concept of lipid metabolism as an active participant in membrane trafficking was ignored during the halcyon days when proteins involved in vesicle biogenesis were being discovered. Since the first demonstrations that specific lipid metabolic pathways are central to these processes (Bankaitis et al, 1990; Cleves et al., 1991), work from numerous laboratories has greatly expanded the lipid–Golgi interface. The report of Schmidt and Brown (2009) adds new sets of activities to the ever-growing roster of lipid metabolic enzymes whose actions contribute to the remarkable Cirque du Soleil of Golgi membrane dynamics. Indeed, we may soon wonder whether there is any such thing as a simple “housekeeping” lipid metabolic pathway in eukaryotic cells.     

Corrélation entre la scintigraphie osseuse et le taux du marqueur tumoral CA15-3 dans le cancer du sein. À propos de 100 cas

AimTo display the correlation between the rate of tumor marker CA15-3 and the bone scintigraphy for extension or supervision check-up in breast cancer.MethodologyIn this study, we have randomly included 100 patients with a serum dosage of CA15-3 and a bone scintigraphy.ResultsWe compared the results of the bone scintigraphy and the rate of CA15-3. Among the 77 patients with elevated CA15-3, 57 presented a bone scintigraphy exhibiting secondary bone locations. Among 23 patients with a normal rate of CA15-3, 18 women presented a normal bone scintigraphy. The sensitivity of bone scintigraphy was estimated at 91.74%, while the specificity was estimated at 47.37%, and calculating the coefficient, which measures the intensity of linking the two variables, CA15-3 and bone scintigraphy, the Yule coefficient was 0.82.ConclusionIn this study, the intensity of the correlation between bone scintigraphy and the rate of CA15-3 proved very strong.     

La theorie du controle du metabolisme controle et regulation

Resume La théorie du Contróle du Métabolisme (Kacser & Bums, 1973; Heinrich & Rapoport, 1974) décrit comment un réseau métabolique répond à de petites perturbations au voisinage d'un état stationnaire. Deux types de coefficients sont définis: les coefficients d'élaslicité qui quantifient les variations des vitesses des étapes isolées et les coefficients de contrôle qui expriment la réponse globale du réseau aux perturbations d'une étape donnée. Des relations entre ces coefficients existent (Relations de sommation et relations de connexion) (pour une revue, voir Mazat et Jean-Bart (1988)).On ne fait pas toujours la distinction entre Contrôle et Régulation. En fait, il apparait que la notion de régulation, si elle est trés claire lorsqu'il s'agit de la régulation de l'activité d'un enzyme, West plus du tout définie lorsqu'il s'agit d'un réseau métabolique dans son ensemble.Le but de l'exposé est de proposer une définition de la régulation d'un réseau métabolique et de montrer quelles relations peuvent exister entre lee phénomènes de régulation et la théorie du contrôle du métabolisme.Quelques exemples seront donnés pour illustration.