Musical training intensity yields opposite effects on grey matter density in cognitive versus sensorimotor networks.

Using optimized voxel-based morphometry, we performed grey matter density analyses on 59 age-, sex- and intelligence-matched young adults with three distinct, progressive levels of musical training intensity or expertise. Structural brain adaptations in musicians have been repeatedly demonstrated in areas involved in auditory perception and motor skills. However, musical activities are not confined to auditory perception and motor performance, but are entangled with higher-order cognitive processes. In consequence, neuronal systems involved in such higher-order processing may also be shaped by experience-driven plasticity. We modelled expertise as a three-level regressor to study possible linear relationships of expertise with grey matter density. The key finding of this study resides in a functional dissimilarity between areas exhibiting increase versus decrease of grey matter as a function of musical expertise. Grey matter density increased with expertise in areas known for their involvement in higher-order cognitive processing: right fusiform gyrus (visual pattern recognition), right mid orbital gyrus (tonal sensitivity), left inferior frontal gyrus (syntactic processing, executive function, working memory), left intraparietal sulcus (visuo-motor coordination) and bilateral posterior cerebellar Crus II (executive function, working memory) and in auditory processing: left Heschl's gyrus. Conversely, grey matter density decreased with expertise in bilateral perirolandic and striatal areas that are related to sensorimotor function, possibly reflecting high automation of motor skills. Moreover, a multiple regression analysis evidenced that grey matter density in the right mid orbital area and the inferior frontal gyrus predicted accuracy in detecting fine-grained incongruities in tonal music.

Preserved capillary density of dorsal finger skin in treated hypertensive patients with or without type 2 diabetes

RESUME : La raréfaction des vaisseaux capillaires est une caractéristique de l'hypertension artérielle non traitée. Des données récentes indiquent que cette raréfaction peut être renversée par un traitement antihypertenseur chez les patients hypertendus non diabétiques. Malgré la fréquente association du diabète et de l'hypertension, on ne sait rien de la densité capillaire de patients diabétiques traités, souffrant d'hypertension artérielle. Nous avons dès lors recruté 21 patients normotendus (groupe contrôle), 25 patients souffrant uniquement d'hypertension artérielle , et 21 patients diabétiques (Diabète de type 2) souffrant également d'hypertension artérielle. Tous les patients hypertendus ont été traités avec un inhibiteur du système rénine-angiotensine, et une majorité présentait une tension artérielle moyenne en auto-contrôle à domicile de 135/85 mmHg ou moins. La densité capillaire a été évaluée par vidéomicroscopie sur la peau du dos des doigts et avec laser Doppler sur la peau de l'avant-bras (vasodilatation maximale induite par le chauffage local). Au final, il n'y avait pas de différence entre les groupes de l'étude, que ce soit lors des mesures de la densité capillaire sur le dos du doigt (groupe contrôle 101 ±11 capillaires, groupe des patients non- diabétiques hypertendus 99 ± 16, groupe des patients hypertendus et diabétiques 96 ± 18, p>0,5) ou lors des mesures de débit sanguin maximal sur la peau de l'avant-bras, un témoin indirect de la densité capillaire dans ce territoire (contrôles 666 ±114 unités de perfusion, non diabétique hypertendu 612 ± 126, hypertendus diabétiques 620 ±103, p> 0,5). En conclusion, notre étude est la première à démontrer que indépendamment de la présence ou non d'un diabète de type 2, la densité capillaire est normale chez les patients hypertendus présentant un contrôle raisonnable de la pression artérielle obtenue avec un bloqueur du système rénine-angiotensine.

Redox dysregulation and oxidative stress in schizophrenia: genetic and functional anomalies of glutathione synthesis in patients and experimental models involving GABA interneurons and NMDA receptors

Objective: Converging evidence speak in favor of an abnormal susceptibility to oxidative stress in schizophrenia. A decreased level of glutathione (GSH), the principal non-protein antioxidant and redox regulator, was observed both in cerebrospinal-fluid and prefrontal cortex of schizophrenia patients (Do et al., 2000). Results: Schizophrenia patients have an abnormal GSH synthesis most likely of genetic origin: Two independent case-control studies showed a significant association between schizophrenia and a GAG trinucleotide repeat (TNR) polymorphism in the GSH key synthesizing enzyme glutamate-cysteine-ligase (GCL) catalytic subunit (GCLC) gene. The most common TNR genotype 7/7 was more frequent in controls, whereas the rarest TNR genotype 8/8 was three times more frequent in patients. The disease-associated genotypes correlated with a decrease in GCLC protein expression, GCL activity and GSH content. Such a redox dysregulation during development could underlie the structural and functional anomalies in connectivity: In experimental models, GSH deficit induced anomalies similar to those observed in patients. (a) morphology: In animal models with GSH deficit during the development we observed in prefrontal cortex a decreased dendritic spines density in pyramidal cells and an abnormal development of parvalbumine (but not of calretinine) immunoreactive GABA interneurones in anterior cingulate cortex. (b) physiology: GSH depletion in hippocampal slices induces NMDA receptors hypofunction and an impairment of long term potentiation. In addition, GSH deficit affected the modulation of dopamine on NMDA-induced Ca 2+ response in cultured cortical neurons. While dopamine enhanced NMDA responses in control neurons, it depressed NMDA responses in GSH-depleted neurons. Antagonist of D2-, but not D1-receptors, prevented this depression, a mechanism contributing to the efficacy of antipsychotics. The redox sensitive ryanodine receptors and L-type calcium channels underlie these observations. (c) cognition: Developing rats with low [GSH] and high dopamine lead deficit in olfactory integration and in object recognition which appears earlier in males that females, in analogy to the delay of the psychosis onset between man and woman. Conclusion: These clinical and experimental evidence, combined with the favorable outcome of a clinical trial with N-Acetyl Cysteine, a GSH precursor, on both the negative symptoms (Berk et al., submitted) and the mismatch negativity in an auditory oddball paradigm supported the proposal that a GSH synthesis impairment of genetic origin represent, among other factors, one major risk factor in schizophrenia.

Stochastic stability and the evolution of coordination in spatially structured populations.

Animals can often coordinate their actions to achieve mutually beneficial outcomes. However, this can result in a social dilemma when uncertainty about the behavior of partners creates multiple fitness peaks. Strategies that minimize risk ("risk dominant") instead of maximizing reward ("payoff dominant") are favored in economic models when individuals learn behaviors that increase their payoffs. Specifically, such strategies are shown to be "stochastically stable" (a refinement of evolutionary stability). Here, we extend the notion of stochastic stability to biological models of continuous phenotypes at a mutation-selection-drift balance. This allows us to make a unique prediction for long-term evolution in games with multiple equilibria. We show how genetic relatedness due to limited dispersal and scaled to account for local competition can crucially affect the stochastically-stable outcome of coordination games. We find that positive relatedness (weak local competition) increases the chance the payoff dominant strategy is stochastically stable, even when it is not risk dominant. Conversely, negative relatedness (strong local competition) increases the chance that strategies evolve that are neither payoff nor risk dominant. Extending our results to large multiplayer coordination games we find that negative relatedness can create competition so extreme that the game effectively changes to a hawk-dove game and a stochastically stable polymorphism between the alternative strategies evolves. These results demonstrate the usefulness of stochastic stability in characterizing long-term evolution of continuous phenotypes: the outcomes of multiplayer games can be reduced to the generic equilibria of two-player games and the effect of spatial structure can be analyzed readily.

Proximal tibia volumetric bone mineral density is correlated to the magnitude of local acceleration in male long distance runners.

Introduction: The beneficial effect of physical exercise on bone mineral density (BMD) is at least partly explained by the forces exerted directly on the bones. Male runners present generally higher BMD than sedentary individuals. We postulated that the proximal tibia BMD is related to the running distance as well as to the magnitude of the shocks (while running) in male runners. Methods: A prospective study (three yearly measurements) included 81 healthy male subjects: 16 sedentary lean subjects and three groups of runners (5-30 km/week, n=19; 30-50 km/week, n=29; 50-100 km/week, n=17). Several measurements were performed at the proximal tibia level: volumetric BMD (vBMD), cortical index (CI) i.e. an index of cortical bone thickness and peak accelerations (an index of shocks during heel strike) while running (measured by a 3-D accelerometer). A general linear model assessed the prediction of vBMD or CI by a) simple effects (running distance, peak accelerations, time) and b) interactions (for instance if vBMD prediction by peak acceleration depends on running distance). Results: CI and vBMD a) increase with running distance to reach a plateau over 30 km/wk, b) are positively associated with peak accelerations over 30 km/week. Discussion: Running may be associated with high peak accelerations in order to have beneficial effects on BMD. More important strains are needed to be associated with the same increase in BMD during running sessions of short duration than those of long duration. Conclusion: CI and vBMD are associated with the magnitude of the shocks during heel strike in runners. Key words: Bone mineral density, strains, physical exercise, running distance.

Low postseroconversion CD4 count and rapid decrease of CD4 density identify HIV+ fast progressors.

CD4 expression in HIV replication is paradoxical: HIV entry requires high cell-surface CD4 densities, but replication requires CD4 down-modulation. However, is CD4 density in HIV+ patients affected over time? Do changes in CD4 density correlate with disease progression? Here, we examined the role of CD4 density for HIV disease progression by longitudinally quantifying CD4 densities on CD4+ T cells and monocytes of ART-naive HIV+ patients with different disease progression rates. This was a retrospective study. We defined three groups of HIV+ patients by their rate of CD4+ T cell loss, calculated by the time between infection and reaching a CD4 level of 200 cells/microl: fast (<7.5 years), intermediate (7.5-12 years), and slow progressors (>12 years). Mathematical modeling permitted us to determine the maximum CD4+ T cell count after HIV seroconversion (defined as "postseroconversion CD4 count") and longitudinal profiles of CD4 count and density. CD4 densities were quantified on CD4+ T cells and monocytes from these patients and from healthy individuals by flow cytometry. Fast progressors had significantly lower postseroconversion CD4 counts than other progressors. CD4 density on T cells was lower in HIV+ patients than in healthy individuals and decreased more rapidly in fast than in slow progressors. Antiretroviral therapy (ART) did not normalize CD4 density. Thus, postseroconversion CD4 counts define individual HIV disease progression rates that may help to identify patients who might benefit most from early ART. Early discrimination of slow and fast progressors suggests that critical events during primary infection define long-term outcome. A more rapid CD4 density decrease in fast progressors might contribute to progressive functional impairments of the immune response in advanced HIV infection. The lack of an effect of ART on CD4 density implies a persistent dysfunctional immune response by uncontrolled HIV infection.

Fracture Discrimination by Combined Bone Mineral Density (BMD) and Microarchitectural Texture Analysis.

The use of bone mineral density (BMD) for fracture discrimination may be improved by considering bone microarchitecture. Texture parameters such as trabecular bone score (TBS) or mean Hurst parameter (H) could help to find women who are at high risk of fracture in the non-osteoporotic group. The purpose of this study was to combine BMD and microarchitectural texture parameters (spine TBS and calcaneus H) for the detection of osteoporotic fractures. Two hundred and fifty five women had a lumbar spine (LS), total hip (TH), and femoral neck (FN) DXA. Additionally, texture analyses were performed with TBS on spine DXA and with H on calcaneus radiographs. Seventy-nine women had prevalent fragility fractures. The association with fracture was evaluated by multivariate logistic regressions. The diagnostic value of each parameter alone and together was evaluated by odds ratios (OR). The area under curve (AUC) of the receiver operating characteristics (ROC) were assessed in models including BMD, H, and TBS. Women were also classified above and under the lowest tertile of H or TBS according to their BMD status. Women with prevalent fracture were older and had lower TBS, H, LS-BMD, and TH-BMD than women without fracture. Age-adjusted ORs were 1.66, 1.70, and 1.93 for LS, FN, and TH-BMD, respectively. Both TBS and H remained significantly associated with fracture after adjustment for age and TH-BMD: OR 2.07 [1.43; 3.05] and 1.47 [1.04; 2.11], respectively. The addition of texture parameters in the multivariate models didn't show a significant improvement of the ROC-AUC. However, women with normal or osteopenic BMD in the lowest range of TBS or H had significantly more fractures than women above the TBS or the H threshold. We have shown the potential interest of texture parameters such as TBS and H in addition to BMD to discriminate patients with or without osteoporotic fractures. However, their clinical added values should be evaluated relative to other risk factors.

Sex differences: From mental rotation to object location memory, an ERP study

Sex differences in cognition have been largely investigated. The most consistent sex differences favoring females are observed in object location memory involving the left hemisphere whereas the most consistent sex differences favoring males are observed in tasks that require mental rotation involving the right hemisphere. Here we used a task involving these two abilities to see the impact of mental rotation on object location memory. To that end we used a combination of behavioral and event-related potential (ERP) electroencephalography (EEG) measures.A computer screen displayed a square frame of 4 pairs of images (a "teddy" bear, a shoe, an umbrella and a lamp) randomly arranged around a central fixation cross. After a 10-second interval for memorization, images disappeared and were replaced by a test frame with no image but a random pair of two locations marked in black. In addition, this test frame was randomly displayed either in the original orientation (0° rotation) or in the rotated one (90° clockwise - CW - or 90° counterclockwise - CCW). Preceding the test frame, an arrow indicating the presence or the absence of rotation of the frame was displayed on the screen. The task of the participants (15 females and 15 males) was to determine if two marked locations corresponded or not to a pair of identical images. Each response was followed by feedback.Findings showed no significant sex differences in the performance of the original orientation. In comparison with this position, the rotation of the frame produced an equal decrease of male and female performance. In addition, this decrease was significantly higher when the rotation of the frame was in a CCW direction. We further assessed the ERP when the arrow indicated the direction of rotation as stimulus-onset, during four time windows representing major components C1, P1, N1 and N2. Although no sex differences were observed in performance, brain activities differed according to sex. Enhanced amplitudes were found for the CCW compared to CW rotation over the right posterior areas for the P1, N1 and N2 components for men as well as for women. Major topographical differences related to sex were measured for the CW rotation condition as marked lateralized amplitude: left-hemisphere amplitude larger than right one was measured during P1 time range for men. These similar patterns prolonged from P1 to N1 for women. Early distinctions were found in interaction with sex between CCW and CW waveform amplitudes, expressing over anterior electrode sites during C1 time range (0-50 ms post-stimulus).In conclusion (i) women do not outperform men in object location memory in this study (absence of rotation condition); (ii) mental rotation, in particular the direction of rotation, influences performance on object location memory; (iii) CCW rotation is associated with activity in the right parietal hemisphere whereas the CW rotation involves the left parietal hemisphere; (iv) this last effect is less pronounced in males, which could explain why greater involvement of right parietal areas in men and of bilateral posterior areas in women is generally reported in mental rotation tasks; and (v) the early distinctions between both directions of rotation located over anterior sites could be related to sex differences in their respective involvement of control mechanisms.

Shifts in species and phylogenetic diversity between sapling and tree communities indicate negative density dependence in a lowland rain forest

1. As trees in a given cohort progress through ontogeny, many individuals die. This risk of mortality is unevenly distributed across species because of many processes such as habitat filtering, interspecific competition and negative density dependence. Here, we predict and test the patterns that such ecological processes should inscribe on both species and phylogenetic diversity as plants recruit from saplings to the canopy. 2. We compared species and phylogenetic diversity of sapling and tree communities at two sites in French Guiana. We surveyed 2084 adult trees in four 1-ha tree plots and 943 saplings in sixteen 16-m2 subplots nested within the tree plots. Species diversity was measured using Fisher's alpha (species richness) and Simpson's index (species evenness). Phylogenetic diversity was measured using Faith's phylogenetic diversity (phylogenetic richness) and Rao's quadratic entropy index (phylogenetic evenness). The phylogenetic diversity indices were inferred using four phylogenetic hypotheses: two based on rbcLa plastid DNA sequences obtained from the inventoried individuals with different branch lengths, a global phylogeny available from the Angiosperm Phylogeny Group, and a combination of both. 3. Taxonomic identification of the saplings was performed by combining morphological and DNA barcoding techniques using three plant DNA barcodes (psbA-trnH, rpoC1 and rbcLa). DNA barcoding enabled us to increase species assignment and to assign unidentified saplings to molecular operational taxonomic units. 4. Species richness was similar between saplings and trees, but in about half of our comparisons, species evenness was higher in trees than in saplings. This suggests that negative density dependence plays an important role during the sapling-to-tree transition. 5. Phylogenetic richness increased between saplings and trees in about half of the comparisons. Phylogenetic evenness increased significantly between saplings and trees in a few cases (4 out of 16) and only with the most resolved phylogeny. These results suggest that negative density dependence operates largely independently of the phylogenetic structure of communities. 6. Synthesis. By contrasting species richness and evenness across size classes, we suggest that negative density dependence drives shifts in composition during the sapling-to-tree transition. In addition, we found little evidence for a change in phylogenetic diversity across age classes, suggesting that the observed patterns are not phylogenetically constrained.

Male reproductive success and multiple paternity in wild, low-density populations of the adder (Vipera berus).

We studied for the first time the occurrence of multiple paternity, male reproductive success, and neonate survival in wild, low-density adder (Vipera berus) populations using 13 microsatellite loci. Paternity was assigned for 15 clutches, collected during 3 years. Our data demonstrated that multiple paternity can occur at a high level (69%) in natural populations of V. berus, even if the density of adults is low. The high proportion of multiple sired clutches was comparable to the proportion observed in captive populations. Male reproductive success significantly increased with body length, and only the largest males successfully sired entire clutches. Finally, no relationship was detected between the number of fathers per clutch and neonate survival. These results suggest that multiple matings could be beneficial in populations with high level of inbreeding or low male fecundity.

Evaluation of Muscardinus avellanarius population density by nest box and by trap checking

Population densities of marked common dormice Muscardinus avellanarius are generally based on nest box checks. As dormice also use natural cavities and leaf nests, we tried to answer the question "what proportion of the population cannot be monitored by nest boy checks", using parallel trapping sessions. We selected a forest of 1.7ha where a 5-year nest box survey revealed an annual mean of 3.4 ± 1.4 dormice per check. The trap design (permanent grid of 77 hanging platforms) was developed in June. During July and August the traps were set every second week (4 sessions of two nights = 8 nights) resulting in a total of 75 captures with mean of 9.4 dormice per night and the presence of 16 different individuals. The grid of 60 nest boxes was checked weekly (8 times) which allowed the recapture of 19 dormice with a mean of 2.4 dormice, per control day and the presence of 6 different individuals. Population density estimated by calendar of capture and the minimal number of dormice alive methods gave for nest-box checks a value of 2.4 animals/ha and the trap checks 6.6 animals/ha with the conclusion that 63% of the population were not being monitored by nest box checks.

Low density lipoprotein signaling and pancreatic beta cells protection

SummaryLow-density lipoproteins (LDLs) have an important physiological role in organism transporting cholesterol and other fatty substances to target tissues. However, elevated LDL levels in the blood are associated with the formation of arterial plaques and consequently atherosclerosis. It is therefore important to characterize the intracellular pathways induced upon LDL stimulation as they might be involved in the pathological properties of these lipoproteins. It has been previously found that LDL stimulation of mouse embryonic fibroblasts activates p38 mitogen activated protein kinases (MAPKs). This leads to cell spreading and increase in the wound healing capabilities of the cells. These two responses might occur within atherosclerotic plaques.The aim of this project is to reveal the missing links between LDL particle and activation of p38 MAPK kinase. As previously shown in our lab activation of p38 MAPK kinase by the LDL particles occur independently of classical LDL receptor (LDLR). In this study we have shown that scavenger receptor type Β class I (SR-BI) is responsible for the signal transduction from the LDLs to the p38 MAPK. We have also shown that Mitogen activated kinase kinases (MKKs) that can directly activate ρ 38 MAPK in these conditions are MKK3 and MKK6 but not MKK4. We have also tested some of the intermediate components of the pathway like Ras and PI3 kinase but found that they do not play a role.The data obtained in this study showed a part of molecular mechanism responsible for p38 MAPK activation and subsequent wound healing and can contribute to our knowledge on function of the fibroblasts in the development of the atherosclerotic plaques.Diabetes Mellitus is a condition caused by disordered metabolism of blood glucose level. It is one of the most commonly spread disease in the western world, with the incidence reaching 8% of population in United States. Two most common types of diabetes are type 1 and 2 that differs slightly in the mechanism of the development. However in the basis of both types lies the cell death of pancreatic beta cells. The aim of this work is to improve beta cells survival in different pathophysiological settings. This could be extrapolated to the conditions in which Diabetes develops in humans. We decided to use RasGAP- derived fragment Ν with its strong antiapoptotic effect in beta cells. In our lab we have demonstrated that in the mild stress conditions RasGAP can be cleaved by caspases at the position 455 producing two fragments, fragment Ν and fragment C. Fragment Ν exerts

Assessment of volumetric bone mineral density of the femoral neck in postmenopausal women with and without vertebral fractures using quantitative multi-slice CT.

OBJECTIVE: To demonstrate the validity and reliability of volumetric quantitative computed tomography (vQCT) with multi-slice computed tomography (MSCT) and dual energy X-ray absorptiometry (DXA) for hip bone mineral density (BMD) measurements, and to compare the differences between the two techniques in discriminating postmenopausal women with osteoporosis-related vertebral fractures from those without. METHODS: Ninety subjects were enrolled and divided into three groups based on the BMD values of the lumbar spine and/or the femoral neck by DXA. Groups 1 and 2 consisted of postmenopausal women with BMD changes <-2SD, with and without radiographically confirmed vertebral fracture (n=11 and 33, respectively). Group 3 comprised normal controls with BMD changes > or =-1SD (n=46). Post-MSCT (GE, LightSpeed16) scan reconstructed images of the abdominal-pelvic region, 1.25 mm thick per slice, were processed by OsteoCAD software to calculate the following parameters: volumetric BMD values of trabecular bone (TRAB), cortical bone (CORT), and integral bone (INTGL) of the left femoral neck, femoral neck axis length (NAL), and minimum cross-section area (mCSA). DXA BMD measurements of the lumbar spine (AP-SPINE) and the left femoral neck (NECK) also were performed for each subject. RESULTS: The values of all seven parameters were significantly lower in subjects of Groups 1 and 2 than in normal postmenopausal women (P<0.05, respectively). Comparing Groups 1 and 2, 3D-TRAB and 3D-INTGL were significantly lower in postmenopausal women with vertebral fracture(s) [(109.8+/-9.61) and (243.3+/-33.0) mg/cm3, respectively] than in those without [(148.9+/-7.47) and (285.4+/-17.8) mg/cm(3), respectively] (P<0.05, respectively), but no significant differences were evident in AP-SPINE or NECK BMD. CONCLUSION: the femoral neck-derived volumetric BMD parameters using vQCT appeared better than the DXA-derived ones in discriminating osteoporotic postmenopausal women with vertebral fractures from those without. vQCT might be useful to evaluate the effect of osteoporotic vertebral fracture status on changes in bone mass in the femoral neck.