Caspase-8 and c-FLIPL associate in lipid rafts with NF-kappaB adaptors during T cell activation.

Humans and mice lacking functional caspase-8 in T cells manifest a profound immunodeficiency syndrome due to defective T cell antigen receptor (TCR)-induced NF-kappaB signaling and proliferation. It is unknown how caspase-8 is activated following T cell stimulation, and what is the caspase-8 substrate(s) that is necessary to initiate T cell cycling. We observe that following TCR ligation, a small portion of total cellular caspase-8 and c-FLIP(L) rapidly migrate to lipid rafts where they associate in an active caspase complex. Activation of caspase-8 in lipid rafts is followed by rapid cleavage of c-FLIP(L) at a known caspase-8 cleavage site. The active caspase.c-FLIP complex forms in the absence of Fas (CD95/APO1) and associates with the NF-kappaB signaling molecules RIP1, TRAF2, and TRAF6, as well as upstream NF-kappaB regulators PKC theta, CARMA1, Bcl-10, and MALT1, which connect to the TCR. The lack of caspase-8 results in the absence of MALT1 and Bcl-10 in the active caspase complex. Consistent with this observation, inhibition of caspase activity attenuates NF-kappaB activation. The current findings define a link among TCR, caspases, and the NF-kappaB pathway that occurs in a sequestered lipid raft environment in T cells.

Fast subplasma membrane Ca2+ transients control exo-endocytosis of synaptic-like microvesicles in astrocytes

Astrocytes are the most abundant glial cell type in the brain. Although not apposite for long-range rapid electrical communication, astrocytes share with neurons the capacity of chemical signaling via Ca(2+)-dependent transmitter exocytosis. Despite this recent finding, little is known about the specific properties of regulated secretion and vesicle recycling in astrocytes. Important differences may exist with the neuronal exocytosis, starting from the fact that stimulus-secretion coupling in astrocytes is voltage independent, mediated by G-protein-coupled receptors and the release of Ca(2+) from internal stores. Elucidating the spatiotemporal properties of astrocytic exo-endocytosis is, therefore, of primary importance for understanding the mode of communication of these cells and their role in brain signaling. We here take advantage of fluorescent tools recently developed for studying recycling of glutamatergic vesicles at synapses (Voglmaier et al., 2006; Balaji and Ryan, 2007); we combine epifluorescence and total internal reflection fluorescence imaging to investigate with unprecedented temporal and spatial resolution, the stimulus-secretion coupling underlying exo-endocytosis of glutamatergic synaptic-like microvesicles (SLMVs) in astrocytes. Our main findings indicate that (1) exo-endocytosis in astrocytes proceeds with a time course on the millisecond time scale (tau(exocytosis) = 0.24 +/- 0.017 s; tau(endocytosis) = 0.26 +/- 0.03 s) and (2) exocytosis is controlled by local Ca(2+) microdomains. We identified submicrometer cytosolic compartments delimited by endoplasmic reticulum tubuli reaching beneath the plasma membrane and containing SLMVs at which fast (time-to-peak, approximately 50 ms) Ca(2+) events occurred in precise spatial-temporal correlation with exocytic fusion events. Overall, the above characteristics of transmitter exocytosis from astrocytes support a role of this process in fast synaptic modulation.

A comparison of electrophysiological changes during the sleep onset period of psychophysiological insomniacs, psychiatric insomniacs and normal sleepers

The EEG of the sleep onset period of psychophysiological insomniacs, psychiatric insomniacs and controls was compared using power spectral analysis (FFT). Eighteen drug-free subjects were equally divided into three groups according to their responses in the Brock Sleep and Insomnia Questionnaire, the Minnesota Multiphasic Personality Inventory and the Sleep Disorders Questionnaire. Group 1 consisted of psychophysiological insomniacs, group 2 included insomniacs with an indication of psychiatric disturbances, and group 3 was a control group. EEG, EOG and EMG were recorded for two consecutive nights. Power spectral analysis (FFT) of EEG at C4 from the sleep onset period (defined as lights out to the first five minutes of stage 2) was performed on all standard frequency bands, delta: .5-4 Hz; theta: 4-8 Hz; alpha: 8-12 Hz; sigma: 12-15 Hz beta: 15-25 Hz. Psychophysiological insomniacs had less alpha during wakefulness than the other two groups and did not show the dramatic drop in alpha across the sleep onset period, which characterizes normal sleep. They also had less delta, especially during stage 2 on night 2. They also showed less delta in the last quartile of the chronological analysis of the sleep onset period. Psychiatric insomniacs showed lower relative beta power values overall while psychophysiological insomniacs showed higher relative beta power values during wakefulness. This microanalysis 11 confirms that the sleep onset period is generally similar for psychiatric insomniacs and normal sleepers. This may be due to the sample of psychiatric insomniacs being heterogeneous or may reflect a sleep onset system that is essentially intact. Psychophysiological insomniacs have higher cortical arousal during the sleep onset period than do the psychiatric insomniacs and the controls. Clear differences in the sleep onset period of psychophysiological insomniacs exist. The dramatic changes in power values in these two groups are not seen in the psychophysiological insomniacs, which may make the discrimination between wakefulness and sleep more difficult.

An electrophysiological examination of intentional and inadvertent sleep onset : the effect of intention on the sleep onset process

The main purpose ofthis study was to examine the effect ofintention on the sleep onset process from an electrophysiological point ofview. To test this, two nap conditions, the Multiple Sleep Latency Test (MSLT) and the Repeated Test of Sustained Wakefulness (RTSW) were used to compare intentional and inadvertent sleep onset. Sixteen female participants (aged 19-25) spent two non-consecutive nights in the sleep lab; however, due to physical and technical difficulties only 8 participants produced compete sets of data for analysis. Each night participants were given six nap opportunities. For three ofthese naps they were instructed to fall asleep (MSLT), for the remaining three naps they were to attempt to remain awake (RTSW). These two types of nap opportunities represented the conditions ofintentional (MSLT) and inadvertent (RTSW) sleep onset. Several other sleepiness, performance, arousal and questionnaire measures were obtained to evaluate and/or control for demand characteristics, subjective effort and mental activity during the nap tests. The nap opportunities were scored using a new 9 stage scoring system developed by Hori et al. (1994). Power spectral analyses (FFT) were also performed on the sleep onset data provided by the two nap conditions. Longer sleep onset latencies (approximately 1.25 minutes) were obseIVed in the RTSW than the MSLT. A higher incidence of structured mental activity was reported in the RTSW and may have been reflected in higher Beta power during the RTSW. The decent into sleep was more ragged in the RTSW as evidenced by an increased number shifts towards higher arousal as measured using the Hori 9 stage sleep scoring method. 1ll The sleep onset process also appears to be altered by the intention to remain awake, at least until the point ofinitial Stage 2 sleep (i.e. the first appearance of spindle activity). When only examining the final 4.3 minutes ofthe sleep onset process (ending with spindle activity), there were significant interactions between the type ofnap and the time until sleep onset for Theta, Alpha and Beta power. That is to say, the pattern of spectral power measurements in these bands differed across time as a function ofthe type ofnap. The effect ofintention however, was quite small (,,2 < .04) when compared to the variance which could be accounted for by the passage oftime (,,2 == .10 to .59). These data indicate that intention alone cannot greatly extend voluntary wakefulness if a person is sleepy. This has serious implications for people who may be required to perform dangerous tasks while sleepy, particularly for people who are in a situation that does not allow them the opportunity to engage in behavioural strategies in order to maintain their arousal.

The role of daytime napping in sleepiness and cognitive function in 24-70 year olds /

Daytime napping improves well-being and performance for young adults. The benefits of napping in older adults should be investigated because they have fragmented nocturnal sleep, cognitive declines, and more opportunity to nap. In addition, experience with napping might influence the benefits of napping. Study 1 examined the role of experience with napping in young adults. Habitual (n = 23) and non-habitual nappers (n = 16) were randomly assigned to a 20-minute nap or a 20- minute reading condition. Both groups slept the same according to macro architecture. However, microarchitecture showed greater theta, alpha, and beta power during Stage 1, and greater delta, alpha, and sigma power during Stage 2 for habitual nappers, for the most part indicating better sleep. Both groups felt less sleepy after the nap. P2 latency, reflecting information processing, decreased after the nap for habitual nappers, and after the control condition for non-habitual nappers. In sum, both groups who slept felt better, but only the habitual nappers who napped gained a benefit in terms of information processing. Based on this outcome, experience with napping was investigated in Study 2. Study 2 examined the extent to which daytime napping enhanced cognition in older adults, especially frontal lobe function. Cognitive deficits in older adults may be due to sleep loss and age-related decline in brain functioning. Longer naps were expected to provide greater improvement, particularly for older adults, by reducing sleep pressure. Thirty-two adults, aged 24-70 years, participated in a repeated measures dose-response manipulation of sleep pressure. Twenty- and sixty-minute naps were compared to a no-nap condition in three age groups. Mood, subjective sleepiness, reaction time, working memory, 11 novelty detection, and waking electro physiological measures were taken before and after each condition. EEG was also recorded during each nap or rest condition. Napping reduced subjective sleepiness, improved working memory (serial addition / subtraction task), and improved attention (reduced P2 amplitude). Physiological sleepiness (i.e., waking theta power) increased following the control condition, and decreased after the longer nap. Increased beta power after the short nap, and seen with older adults overall, may have reflected increased mental effort. Older adults had longer latencies and smaller amplitudes for several event-related potential components, and higher beta and gamma power. Following the longer nap, gamma power decreased for older adults, but increased for young adults. Beta and gamma power may represent enhanced alertness or mental effort. In addition, Nl amplitude showed that benefits depend on the preceding nap length as well as age. Since the middle group had smaller Nl amplitudes following the short nap and rest condition, it is possible that they needed a longer nap to maintain alertness. Older adults did not show improvements to Nl amplitude following any condition; they may have needed a nap longer than 60 minutes to gain benefits to attention or early information processing. Sleep characteristics were not related to benefits of napping. Experience with napping was also investigated. Subjective data confirmed habitual nappers were happier to nap, while non-habitual nappers were happier to stay awake, reflecting self-identified napping habits. Non-habitual nappers were sleepier after a nap, and had faster brain activity (i.e., heightened vigilance) at sleep onset. These reasons may explain why non-habitual nappers choose not to nap.

The effects of simple procedural, cognitive procedural and declarative learning on sleep /

Sleep spindles have been found to increase following an intense period of learning on a combination of motor tasks. It is not clear whether these changes are task specific, or a result of learning in general. The current study investigated changes in sleep spindles and spectral power following learning on cognitive procedural (C-PM), simple procedural (S-PM) or declarative (DM) learning tasks. It was hypothesized that S-PM learning would result in increases in Sigma power during Non-REM sleep, whereas C-PM and DM learning would not affect Sigma power. It was also hypothesized that DM learning would increase Theta power during REM sleep, whereas S-PM and C-PM learning would not affect Theta power. Thirty-six participants spent three consecutive nights in the sleep laboratory. Baseline polysomnographic recordings were collected on night 2. Participants were randomly assigned to one of four conditions: C-PM, S-PM, DM or control (C). Memory task training occurred on night 3 followed by polysomnographic recording. Re-testing on respective memory tasks occurred one-week following training. EEG was sampled at 256Hz from 16 sites during sleep. Artifact-free EEG from each sleep stage was submitted to power spectral analysis. The C-PM group made significantly fewer errors, the DM group recalled more, and the S-PM improved on performance from test to re-test. There was a significant night by group interaction for the duration of Stage 2 sleep. Independent t-tests revealed that the S-PM group had significantly more Stage 2 sleep on the test night than the C group. The C-PM and the DM group did not differ from controls in the duration of Stage 2 sleep on test night. There was no significant change in the duration of slow wave sleep (SWS) or REM sleep. Sleep spindle density (spindles/minute) increased significantly from baseline to test night following S-PM learning, but not for C-PM, DM or C groups. This is the first study to have shown that the same pattern of results was found for spindles in SWS. Low Sigma power (12-14Hz) increased significantly during SWS following S-PM learning but not for C-PM, DM or C groups. This effect was maximal at Cz, and the largest increase in Sigma power was at Oz. It was also found that Theta power increased significantly during REM sleep following DM learning, but not for S-PM, C-PM or C groups. This effect was maximal at Cz and the largest change in Theta power was observed at Cz. These findings are consistent with the previous research that simple procedural learning is consolidated during Stage 2 sleep, and provide additional data to suggest that sleep spindles across all non-REM stages and not just Stage 2 sleep may be a mechanism for brain plasticity. This study also provides the first evidence to suggest that Theta activity during REM sleep is involved in memory consolidation.

A microanalysis of EMG and EEG changes during the sleep onset period (SOP) : a theoretical investigation with practical applications /

The present study has both theoretical and practical aspects. The theoretical intent of the study was to closely examine the relationship between muscle activity (EMG) and EEG state during the process of falling asleep. Sleep stages during sleep onset (SO) have been generally defined with regards to brain wave activity (Recht schaff en & Kales (1968); and more precisely by Hori, Hayashi, & Morikawa (1994)). However, no previous study has attempted to quantify the changes in muscle activity during this same process. The practical aspect of the study examined the reliability ofa commercially developed wrist-worn alerting device (NovAlert™) that utilizes changes in muscle activity/tension in order to alert its user in the event that he/she experiences reduced wakefulness that may result in dangerous consequences. Twelve female participants (aged 18-42) sp-ent three consecutive nights in the sleep lab ("Adaptation", "EMG", and "NOVA" nights). Each night participants were given 5, twenty-minute nap opportunities. On the EMG night, participants were allowed to fall asleep freely. On the NOV A night, participants wore the Nov Alert™ wrist device that administered a Psychomotor Vigilance Test (PVT) when it detected that muscle activity levels had dropped below baseline. Nap sessions were scored using Hori's 9-stage scoring system (Hori et aI, 1994). Power spectral analyses (FFT) were also performed. Effects ofthe PVT administration on EMG and EEG frequencies were also examined. Both chin and wrist EMG activity showed reliable and significant decline during the early stages ofHori staging (stages HO to H3 characterized by decreases in alpha activity). All frequency bands studied went through significant changes as the participants progressed through each ofHori's 9 SO stages. Delta, theta, and sigma activity increased later in the SO continuum while a clear alpha dominance shift was noted as alpha activity shifted from the posterior regions of the brain (during Hori stages HO to H3) to the anterior portions (during Hori stages H7 to H9). Administration of the PVT produced significant increases in EMG activity and was effective in reversing subjective drowsiness experienced during the later stages of sleep onset. Limitations of the alerting effects of the PVTs were evident following 60 to 75 minutes of use in that PVTs delivered afterwards were no longer able to significantly increase EMG levels. The present study provides a clearer picture of the changes in EMG and EEG during the sleep onset period while testing the efficacy of a commercially developed alerting device. EMG decreases were found to begin during Hori stage 0 when EEG was - dominated by alpha wave activity and were maximal as Hori stages 2 to 5 were traversed (coincident with alpha and beta activity). This signifies that EMG decrements and the loss of resting alpha activity are closely related. Since decreased alpha has long been associated with drowsiness and impending sleep, this investigation links drops in muscle tone with sleepiness more directly than in previous investigations. The EMG changes were reliably demonstrated across participants and the NovAlert™ detected the EMG decrements when Hori stage 3 was entered. The alerting vibrations produced by the NovAlert™ occurred early enough in the SO process to be of practical importance as a sleepiness monitoring and alerting device.

The Role of Sleep in the Selective Reconsolidation of Declarative Memories

While sleep has been shown to be involved in memory consolidation and the selective enhancement of newly acquired memories of future relevance (Wilhelm, et al., 2011), limited research has investigated the role of sleep or future relevance in processes of memory reconsolidation. The current research employed a list-method directed forgetting procedure in which participants learned two lists of syllable pairs on Night 1 and received directed forgetting instructions on Night 2. On Night 2, one group (Labile; n = 15) received a memory reactivation treatment consisting of reminders designed to return memories of the learned lists to a labile state. A second group (Stable, n = 16) received similar reminders designed to leave memories of the learned lists in their stable state. No differences in forgetting were found across the two lists or groups. However, a negative correlation between frontal delta (1 – 4 Hz) electroencephalographic (EEG) power during Early Stage 2 non-rapid eye movement (NREM) sleep and forgetting of to-beremembered material was found exclusively in the Labile group (r = -.61, p < .05). Further, central theta (4 – 8 Hz ) EEG power during rapid eye movement (REM) sleep was found to correlate with directed forgetting exclusively in the Labile group (r = .81, p < .001) and total forgetting in the Stable group (r = .50, p < .05). These observed relationships support the proposed hypothesis suggesting that sleep processes are involved in the reconsolidation of labile memories, and that this reconsolidation may be selective for memories of future relevance. A role for sleep in the beneficial reprocessing of memories through the selective reconsolidation of labile memories in NREM sleep and the weakening of memories in REM sleep is discussed.

Genetic and Electrophysiological Correlates of Self-Regulation in Adolescence

Self-regulation is considered a powerful predictor of behavioral and mental health outcomes during adolescence and emerging adulthood. In this dissertation I address some electrophysiological and genetic correlates of this important skill set in a series of four studies. Across all studies event-related potentials (ERPs) were recorded as participants responded to tones presented in attended and unattended channels in an auditory selective attention task. In Study 1, examining these ERPs in relation to parental reports on the Behavior Rating Inventory of Executive Function (BRIEF) revealed that an early frontal positivity (EFP) elicited by to-be-ignored/unattended tones was larger in those with poorer self-regulation. As is traditionally found, N1 amplitudes were more negative for the to-be-attended rather than unattended tones. Additionally, N1 latencies to unattended tones correlated with parent-ratings on the BRIEF, where shorter latencies predicted better self-regulation. In Study 2 I tested a model of the associations between selfregulation scores and allelic variations in monoamine neurotransmitter genes, and their concurrent links to ERP markers of attentional control. Allelic variations in dopaminerelated genes predicted both my ERP markers and self-regulatory variables, and played a moderating role in the association between the two. In Study 3 I examined whether training in Integra Mindfulness Martial Arts, an intervention program which trains elements of self-regulation, would lead to improvement in ERP markers of attentional control and parent-report BRIEF scores in a group of adolescents with self-regulatory difficulties. I found that those in the treatment group amplified their processing of attended relative to unattended stimuli over time, and reduced their levels of problematic behaviour whereas those in the waitlist control group showed little to no change on both of these metrics. In Study 4 I examined potential associations between self-regulation and attentional control in a group of emerging adults. Both event-related spectral perturbations (ERSPs) and intertrial coherence (ITC) in the alpha and theta range predicted individual differences in self-regulation. Across the four studies I was able to conclude that real-world self-regulation is indeed associated with the neural markers of attentional control. Targeted interventions focusing on attentional control may improve self-regulation in those experiencing difficulties in this regard.

Evaluating Knowledge of a Function-based Cognitive-Behavioural Treatment for Obsessive Compulsive Behaviour in Autism Spectrum Disorder

Children with Autism Spectrum Disorder (ASD) have restricted and repetitive behaviours (RRBs) which may be similar to obsessions and compulsions in Obsessive Compulsive Disorder (OCD). These behaviours can be intrusive and interfere in the lives of the child and their family. Preliminary studies have shown success in using adapted Cognitive Behavioural Therapy (CBT) to treat these behaviors in children with high functioning ASD. Using a hypothetical vignette, this thesis attempted to examine procedural knowledge that the children and their parents gained while participating in a CBT treatment that was evaluated in a Randomized Controlled Trial. For both parents and children, there was a significant increase in number of strategies generated from pre to post-treatment. Further, children in the experimental group generated significantly more strategies than the treatment as usual (TAU) group post-intervention. There was no significant correlation between number of strategies generated and the child’s treatment success, age, or IQ.

A domain-general perspective on medial frontal brain activity during performance monitoring

Activity of the medial frontal cortex (MFC) has been implicated in attention regulation and performance monitoring. The MFC is thought to generate several event-related potential (ERPs) components, known as medial frontal negativities (MFNs), that are elicited when a behavioural response becomes difficult to control (e.g., following an error or shifting from a frequently executed response). The functional significance of MFNs has traditionally been interpreted in the context of the paradigm used to elicit a specific response, such as errors. In a series of studies, we consider the functional similarity of multiple MFC brain responses by designing novel performance monitoring tasks and exploiting advanced methods for electroencephalography (EEG) signal processing and robust estimation statistics for hypothesis testing. In study 1, we designed a response cueing task and used Independent Component Analysis (ICA) to show that the latent factors describing a MFN to stimuli that cued the potential need to inhibit a response on upcoming trials also accounted for medial frontal brain responses that occurred when individuals made a mistake or inhibited an incorrect response. It was also found that increases in theta occurred to each of these task events, and that the effects were evident at the group level and in single cases. In study 2, we replicated our method of classifying MFC activity to cues in our response task and showed again, using additional tasks, that error commission, response inhibition, and, to a lesser extent, the processing of performance feedback all elicited similar changes across MFNs and theta power. In the final study, we converted our response cueing paradigm into a saccade cueing task in order to examine the oscillatory dynamics of response preparation. We found that, compared to easy pro-saccades, successfully preparing a difficult anti-saccadic response was characterized by an increase in MFC theta and the suppression of posterior alpha power prior to executing the eye movement. These findings align with a large body of literature on performance monitoring and ERPs, and indicate that MFNs, along with their signature in theta power, reflects the general process of controlling attention and adapting behaviour without the need to induce error commission, the inhibition of responses, or the presentation of negative feedback.

The Effects of Magnetic Dilution and Applied Pressure on Several Frustrated Spinels

The effects of magnetic dilution and applied pressure on frustrated spinels GeNi2O4, GeCo2O4, and NiAl2O4 are reported. Dilution was achieved by substitution of Mg2+ in place of magnetically active Co2+ and Ni2+ ions. Large values of the percolation thresholds were found in GeNi(2-x)MgxO4. Specifically, pc1 = 0.74 and pc2 = 0.65 in the sub-networks associated with the triangular and kagome planes, respectively. This anomalous behaviour may be explained by the kagome and triangular planes behaving as coupled networks, also know as a network of networks. In simulations of coupled lattices that form a network of networks, similar anomalous percolation threshold values have been found. In addition, at dilution levels above x=0.30, there is a T^2 dependency in the magnetic heat capacity which may indicate two dimensional spin glass behaviour. Applied pressures in the range of 0 GPa to 1.2 GPa yield a slight decrease in ordering temperature for both the kagome and triangular planes. In GeCo(2-x)MgxO4, the long range magnetic order is more robust with a percolation threshold of pc=0.448. Similar to diluted nickel germanate, at low temperatures, a T^2 magnetic heat capacity contribution is present which indicates a shift from a 3D ordered state to a 2D spin glass state in the presence of increased dilution. Dynamic magnetic susceptibility data indicate a change from canonical spin glass to a cluster glass behaviour. In addition, there is a non-linear increase in ordering temperature with applied pressure in the range P = 0 to 1.0 GPa. A spin glass ground state was observed in Ni(1-x)MgxAl2O4 for (x=0 to 0.375). Analysis of dynamic magnetic susceptibility data yield a characteristic time of tau* = 1.0x10^(-13) s, which is indicative of canonical spin glass behaviour. This is further corroborated by the linear behaviour of the magnetic specific heat contribution. However, the increasing frequency dependence of the freezing temperature suggests a trend towards spin cluster glass formation.

Niveaux de vitamine a (retinol et acide retinoïque) mesurés dans le sang de cordon ombilical et dévéloppement rénal des nouveau-nés

Introduction : La Vitamine A (rétinol, ROL) et son métabolite l’acide rétinoïque (AR) sont essentielles pour l’embryogénèse. L’excès comme l’insuffisance d’AR sont nocives. L’AR est régularisé dans l’embryon par des gènes spécifiques (ALDH, CRABP, CYP). Hypothèse : Les grandes variations d’AR dans le plasma des adultes normaux, nous ont orienté à mesurer les rétinoïdes (ROL et RA) dans le sang de cordon ombilical, pour évaluer des corrélations avec des polymorphismes des gènes impliquées dans le métabolisme de l’AR et le développement rénal-(RALDH2, CRABP2, CYP26A1; B1). Vérifier pour des corrélations entre ces rétinoïdes et/ou avec la taille de reins à la naissance. Méthodes : Extraction du ROL et RA du sang de cordon ombilical de 145 enfants et analyse par HPLC. Le volume des reins a été mesuré par ultrasonographie et l’ADN génomique leucocytaire extrait (FlexiGene DNA-Kit). 10 échantillons d’ADN ont été exclus (qualité). Les htSNP : ALDH1A2, CRABP2, CYP26A1;B1 du génome humain (HapMap) ont été séquencés et génotypés (Sequenom iPlex PCR).Des testes bio-statistiques des fréquences génotypiques et alléliques ont été effectués (Single-Locus, χ2, Kruskal-Wallis, Allelic-Exact).Des corrélations (ROL, RA, SNPs, V-reins) ont été analysés (Kendall-tau /Oakes). Résultats : La Δ RA (0.07-550.27 nmol/l) non corrélé avec la Δ ROL (51.39-3892.70 nmol/l). Il n’y a pas d’association ROL ou RA avec les volumes des reins ou avec les SNPs/ CYP21A1;B1. Corrélations trouvées : 1. (p=0.035), polymorphisme génétique ALDH1A2-SNP (rs12591551:A/C) hétérozygote/CA, (25enfants, 19%) avec moyennes d’AR (62.21nmol/l). 2. (p=0.013), polymorphisme CRABP2-SNP (rs12724719:A/G) homozygote/AA (4 enfants, 3%) avec hautes valeurs moyennes d’AR (141,3 nmol/l). Discussion-Conclusion : Les grandes ΔRA suggèrent une variabilité génique individuelle du métabolisme de ROL. Les génotypes (CA)-ALDH1A2/ SNP (rs12591551:A/C) et (AA) -CRABP2/SNP (rs12724719:A/G) sont associés à des valeurs moyennes hautes d’AR, pouvant protéger l’embryogénèse lors d’une hypovitaminose A maternelle.