Nonlinear self-trapping of matter waves in periodic potentials.

We report the first experimental observation of nonlinear self-trapping of Bose-condensed 87Rb atoms in a one-dimensional waveguide with a superimposed deep periodic potential . The trapping effect is confirmed directly by imaging the atomic spatial distribution. Increasing the nonlinearity we move the system from the diffusive regime, characterized by an expansion of the condensate, to the nonlinearity dominated self-trapping regime, where the initial expansion stops and the width remains finite. The data are in quantitative agreement with the solutions of the corresponding discrete nonlinear equation. Our results reveal that the effect of nonlinear self-trapping is of local nature, and is closely related to the macroscopic self-trapping phenomenon already predicted for double-well systems.

Signaling pathways leading to apoptosis or survival in immature and mature B cells.

In the absence of phosphorylated Gab2, immature B cells are unable to maintain a prolonged signal transduction, which is necessary for the transcriptional regulation and activation of the cells. Thus, the lack of Gab2 phosphorylation may drive immature B cells to apoptosis.

Unregulated activation of STAT-5, ERK1/2 and c-Fos may contribute to the phenotypic transformation from myelodysplastic syndrome to acute leukaemia.

Myelodysplastic syndrome (MDS) is characterised by ineffective erythropoiesis and poor progenitor response to erythropoietin (Epo). The aim of this study was to determine the role of the Epo-R mediated signalling in the rise of MDS and whether alteration of signalling pathways contribute to the leukeamogenesis from MDS to acute leukaemia. We analysed Epo and GM-CSF induced ERK1/2 activation, c-Fos expression, STAT-5 and AP-1 DNA binding activities in mononuclear cells of umbilical cord blood (UCBMNC), normal marrow (NBMMNC) or marrow with MDS, AML with prior MDS and de novo AML. In UCBMNC and NBMMNC, Epo and GM-CSF induced the activation of STAT-5 DNA binding and ERK 1/2 activation (n = 6). In contrast, in MDS RA, both signalling pathways were activated only by GM-CSF but not by Epo (n = 7). In acute leukaemia, elevated basal activity of STAT-5 DNA binding appeared in 8/8 cases, which was independent of Epo or GM-CSF treatment. In normal and MDS samples, c-Fos and Egr-1 proteins were not detectable and the expression levels were not increased by Epo or GM-CSF treatment. In contrast, we found an elevated level of c-Fos expression in 5/8 acute leukemia cases, which was not further increased in the presence of Epo or GM-CSF. The elevated c-Fos expression was accompanied by an extremely high blast number in 5/5 cases. These results suggest that impaired ERK/MAPK activation, similarly to impaired STAT-5 activation in Epo-R signalling, may be responsible for the apoptotic process and the block of maturation in MDS RA. The results also suggest that the appearance of the constitutively activated STAT-5 DNA binding and c-Fos expression may be used as a predictor of the blastic transformation.

Activation of Raf/ERK1/2 MAP kinase pathway is involved in GM-CSF-induced proliferation and survival but not in erythropoietin-induced differentiation of TF-1 cells.

The involvement of MAPK pathways in differentiation, proliferation and survival was investigated by comparing Epo and GM-CSF signalling in human factor-dependent myeloerythroid TF-1 cells with abnormal Epo-R. GM-CSF withdrawal induced cell-cycle arrest and apoptosis accompanied by increased caspase-3 activity, DNA degradation and reduced expression of the antiapoptotic Bcl-2 and Bcl-xl proteins. Readministration of GM-CSF but not Epo reversed these processes and induced proliferation. The GM-CSF promoted cell survival and proliferation correlated with MEK-1 dependent ERK1/2, Elk-1 and CREB phosphorylation and Egr-1, c-Fos expression as well as with increased STAT-5, AP-1, c-Myb and NF-kappaB DNA-binding. In contrast, Epo failed to activate the Raf-1/ERK1/2 MAPK pathway or to induce Egr-1 and/or c-Fos expression, while it induced erythroid differentiation in GM-CSF-deprived cells. In addition, the Epo-induced haemoglobin production was inhibited in the presence of GM-CSF. These results demonstrate that the activation of MAPK cascade is not necessary for Epo-induced haemoglobin production in TF-1 cells and suggest a negative cross-talk between the signalling of GM-CSF-stimulated cell proliferation and Epo-induced erythroid differentiation.

Signalling mechanisms and the role of calcineurin in erythropoiesis.

Erythropoietin (Epo) is the principal regulator of the production of circulating erythrocytes by controlling the proliferation, the differentiation and the survival of the erythroid progenitor cells. Early down-regulation of c-myb expression in erythroleukemia cells is a common feature of the action of Epo and chemical inducers of differentiation such as DMSO. Previously we have shown that in our Epo-responsive murine erythroleukemia cell line ELM-I-1, [Ca2+]i increasing agents can mimic the effect of Epo on c-myb expression and activate nuclear signal transduction processes involved in the induction of hemoglobin synthesis. These results also indicated that the Ca2+-induced down-regulation of c-myb expression and hemoglobin synthesis are mediated by the Ca2+/calmodulin dependent serine/threonine-specific protein phosphatase PP2B, calcineurin, but the Epo induced processes are not mediated by PP2B. In spite of this, we demonstrated in this paper that in ELM-I-1 cells the Epo-induced down-regulation of c-myb expression and hemoglobin production can be effectively enhanced by the simultaneously added [Ca2+]i-increasing agent, cyclopiazonic acid (CPA). This observation further supports the existence of at least two independent signalling pathways in the mechanism of Epo and [Ca2+]i increasing agents and the strong correlation between c-myb expression and hemoglobin production in differentiating cells. Although the c-AMP-response element binding protein (CREB) could be the common target of both calcium-dependent and -independent dephosphorylation, our results do not support the involvement of CREB in the regulation of c-myb gene expression. In addition to the calcineurin mediated down-regulation of c-myb expression, we have found a negative regulatory effect in the Ca2+-mediated transcriptional activation of certain genes. In response to [Ca2+]i-increasing agents in ELM-I-1 cells, both, egr-1 and c-fos mRNA expression increased significantly after the inhibition of calcineurin by cyclosporine A. Cyclosporin A exerted stimulatory effects on the egr-1 and c-fos expression also at lower (150-400 nM) intracellular Ca2+ levels. This potential co-regulation of c-myb, egr-1 and c-fos expression by calcineurin suggests that the negative modulation of egr-1 and c-fos expression may also be important for the induction of erythroid differentiation by [Ca2+]i-increasing agents. This negative modulation may also contribute to the Epo-induced differentiation in the case of a moderate increase of [Ca2+]i.

[The distribution of sleep and wakefulness in human African trypanosomiasis]. / Distribution du sommeil et de la veille dans la trypanosomose humaine africaine.

Last century, patients with human African trypanosomiasis were described as sleepy by day and restless by night, and physicians referred to this condition as sleeping sickness. Such a description could have evoked a disturbance of circadian rhythms. However, it is only in 1989 that the first 24-hour recording was performed by our team in Niamey (Niger) in a patient with sleeping sickness. The patient was a Niger-born farm worker who had contracted the disease near Gagnoa (Côte d'Ivoire). Polysomnographic recordings (electroencephalogram, EEG, electrooculogram, electromyogram, electrocardiogram, buccal and nasal airflow, and chest respiratory movements) showed a disappearance of the circadian distribution of sleep and wakefulness, which tended to occur evenly throughout day and night, with a sleep-wake alternation of approximately 80 minutes. Two investigations were conducted thereafter. The first one was done at Daloa (Côte d'Ivoire) in 8 patients who were recorded during two 24-hour periods, with and without hourly blood samples; the second at Brazzaville (Congo) in 10 patients recorded for 24 hours before and after treatment with melarsoprol. All patients were at the stage of early meningoencephalitis. At Daloa, polysomnographic recordings were taken on two 8-channel EEG machines (Alvar Minihuit, and T3-ECEM), as well as on a portable Oxford Medilog 9000 system from the same electrodes. Sleep and wake structure was altered in the most severely sick patient, the EEG trace being loaded with slow waves. Stages 1 and 2, and stages 3 and 4 could not be distinguished from one another. In the other patients, all sleep stages were easily scored. No difference was seen between recordings, regarding blood collection.(ABSTRACT TRUNCATED AT 250 WORDS)

Study of evoked potentials in human African trypanosomiasis.

Human African trypanosomiasis or sleeping sickness has a stage of neurological involvement characterized by the onset of diffuse meningoencephalitis with sleep disturbances and decreased wakefulness. The pathogenesis of this disease is not well understood. We studied auditory, visual, sensory, and motor evoked potentials in 16 patients with trypanosomiasis in the early stage of meningoencephalitis. In all patients, the brain-stem auditory evoked response (BAER) and the pattern-reversal visual evoked response (PVER) were normal. On the other hand, abnormalities of the somatosensory evoked response (SSER) or the motor evoked response (MER) were found in only five cases; however, their relationship to the illness could not be definitely confirmed. The study results indicate that the evaluated pathways were essentially intact, in particular at the level of the brain-stem in the early stage of the disease. Sleep disturbances and decreased wakefulness noted at this stage were thus linked more closely to functional involvement at the level of the sleep centres than to any detectable specific anatomic lesion.

[Transitory eye pain during sleep]. / Oculalgie transitoire pendant le sommeil.

Transitory eye pain occurred during sleep in a 62 year-old patient, who complained of being often awoken during the second half of the night. Diurnal ophthalmologic examinations did not reveal any abnormality. Three consecutive nocturnal polysomnographic recordings were performed to determine whether these pain crises were related to any sleep stage. The patient woke up three times during the recordings because of the usual pain occurrence. On the three occasions, the crisis occurred during of immediately after a REM sleep phase. The brievity of the pain episode (4 to 5 min) did not allow a quick eye pressure measurement to demonstrate a possible increase in ocular tension. However, the role of the REM sleep myosis and vegetative manifestations are discussed regarding the determination of eye pain.

[Circadian analysis of sleep, rectal temperature and immunological and endocrinological variables in sleeping sickness: preliminary study]. / Analyse circadienne du sommeil, de la température rectale et de variables immunologiques et endocrinologiques dans la maladie du sommeil: etude préliminaire.

A multidisciplinary study was conducted in 8 patients with neurological Human African Trypanosomiasis. The sleep-wake cycle followed an ultradian pattern which was more pronounced in patients with more severe symptoms. The EEG trace was consistently interrupted by numerous cyclic activation patterns with K complexes, rapid low amplitude elements and slow high voltage elements. Circadian rhythmicity was also disturbed in other physiological (rectal temperature), immunological (interleukins) or hormonal (cortisol, prolactin) variables, the disturbance being greater in severely hit patients.

Thermal exchanges during sleep in anhidrotic ectodermal dysplasia.

Anhidrotic ectodermal dysplasia is a congenital syndrome characterized by the absence of sweat glands. A sweating test was performed on such a patient and proved his inability to sweat. Thermal exchanges during night sleep were then measured in this patient and compared with data obtained from a healthy control subject. Ambient conditions were as follows: dry bulb temperature 32.2 degrees C, relative humidity 30%-40%, wind speed 0.7 m.s-1. Polysomnographic recordings showed normal sleep patterns in both subjects, but a "first night effect" in the patient. Rectal (Tre) and mean skin (Tsk) temperatures and loss of mass were monitored continuously throughout the 8-h sleep recording. Loss of mass averaged 34.1 g.h-1 in the patient vs 78.1 g.h-1 in the control subject. No relationship with sleep stages was observed in the patient, in contrast to the control subject who experienced a decrease in evaporation during rapid eye movement sleep. Body temperatures varied little in the patient, but decreased until the 6th h of sleep in the control subject. On two occasions there was a 0.3 degrees C fall in the Tre of the patient during two slow wave sleep (SWS) phases, while Tsk and loss of mass did not change. As thermolytic processes had not varied on these two occasions, it was concluded that the fall in Tre indicated a concomitant decrease in metabolic heat production, in agreement with the assumption that SWS represented a state of energy conservation.

24 hour polysomnographic evaluation in a patient with sleeping sickness.

A 24 h polysomnographic recording was performed in a patient with sleeping sickness presenting an atypical neurological syndrome. Trypanosoma gambiense was found in a lymph gland puncture and the CSF, and a serologic immunofluorescence test was positive. The scoring technique of the polygraphic traces had to be adapted because of the presence of a permanent EEG delta wave activity during the NREM sleep stages, and the method used by Schwartz and Escande (1970) was applied. REM sleep and wakefulness presented normal polygraphic characteristics. The patient had 8 sleep episodes throughout the recording period, occurring during the daytime and at night, forming the classical diurnal sleepiness and nocturnal restlessness of sleeping sickness. All but one episode represented 1-3 complete REM-NREM sleep cycles. On all occasions, REM latency was short and 2 SOREM episodes were observed. The nychthemeral organization of the stages of vigilance differed from one state to another. Wakefulness and REM sleep had a circadian rhythmicity, while NREM sleep, total sleep time and deep sleep (corresponding to stages 3 and 4) had an ultradian periodicity. The concordance between the higher pressure for wakefulness and lower pressure for sleep around 20.00 h defined the time of occurrence of a 'forbidden zone' for sleep.

Seasonal changes in circadian rhythms of body temperatures in humans living in a dry tropical climate.

Seven volunteers (3 females and 4 males; 3 Caucasians and 4 Africans) participated in two 24 h sessions during the cool dry (CD) and the hot dry (HD) seasons of the sahelian tropical climate. Body temperatures were taken on portable cassette recorders for 24 h. Rectal (Tre) and mean skin (Tsk) temperatures decreased in the HD compared to the CD conditions, meeting one of the criteria for adaptation to heat. No ethnic differences in thermal responses were found. Males and females differed in their body temperature rhythms and in their reactions to heat. Body temperatures were higher in females than in males. Males reacted to heat with a decrease in Tre, without change in the Tre-Tsk gradient. Females showed a decrease in both Tre and Tsk, more marked for Tsk, with an increase in the Tre-Tsk gradient. It was concluded that males showed seasonal acclimatization to heat via a decrease in metabolism confirmed by a decrease in plasma levels of thyroid stimulating hormone (TSH) in the HD condition. Females showed a mixed metabolic and thermolytic type of acclimatization, with an absence of variation in plasma TSH levels. In conclusion, the steady rise in temperature between the CD and HD conditions was sufficient to trigger an acclimatization to heat similar in Caucasian and African subjects, although exposure to the external climate differed widely.