Take it or leave it: prefrontal control in recreational cocaine users.

Though stimulant drugs such as cocaine are considered highly addictive, some individuals report recreational use over long periods without developing dependence. Difficulties in response inhibition have been hypothesized to contribute to dependence, but previous studies investigating response inhibition in recreational cocaine users have reported conflicting results. Performance on a stop-signal task was examined in 24 recreational cocaine users and 32 healthy non-drug using control participants matched for age, gender and verbal intelligence during functional magnetic resonance imaging scanning. The two groups were further matched on traumatic childhood histories and the absence of family histories of addiction. Results revealed that recreational cocaine users did not significantly differ from controls on any index of task performance, including response execution and stop-signal reaction time, with the latter averaging 198 ms in both groups. Functional magnetic resonance imaging analyses indicated that, compared with controls, stopping in the recreational users was associated with increased activation in the pre-supplementary motor area but not the right inferior frontal cortex. Thus, findings imply intact response inhibition abilities in recreational cocaine users, though the distinct pattern of accompanying activation suggests increased recruitment of brain areas implicated in response inhibition. This increased recruitment could be attributed to compensatory mechanisms that enable preserved cognitive control in this group, possibly relating to their hypothetical resilience to stimulant drug dependence. Such overactivation, alternatively, may be attributable to prolonged cocaine use leading to neuroplastic adaptations.This work was funded by a Medical Research Council (MRC) research grant to KDE, ETB and TWR (G0701497) and was conducted within the Behavioural and Clinical Neuroscience Institute, University of Cambridge, UK, which is supported by a joint award from the MRC and the Wellcome Trust; Both KDE and PSJ were supported by the MRC, SM was supported by a Wellcome Trust grant (089589/Z/09/Z) awarded to TW Robbins.This is the final version of the article. It first appeared from NPG via http://dx.doi.org/10.1038/tp.2015.8

Physicochemical analysis of rotavirus segment 11 supports a 'modified panhandle' structure and not the predicted alternative tRNA-like structure (TRLS)

.Rotaviruses are a major cause of acute gastroenteritis, which is often fatal in infants. The viral genome consists of 11 double-stranded RNA segments, but little is known about their cis-acting sequences and structural elements. Covariation studies and phylogenetic analysis exploring the potential structure of RNA11 of rotaviruses suggested that, besides the previously predicted "modified panhandle" structure, the 5' and 3' termini of one of the isoforms of the bovine rotavirus UKtc strain may interact to form a tRNA-like structure (TRLS). Such TRLSs have been identified in RNAs of plant viruses, where they are important for enhancing replication and packaging. However, using tRNA mimicry assays (in vitro aminoacylation and 3'- adenylation), we found no biochemical evidence for tRNA-like functions of RNA11. Capping, synthetic 3' adenylation and manipulation of divalent cation concentrations did not change this finding. NMR studies on a 5'- and 3'-deletion construct of RNA11 containing the putative intra-strand complementary sequences supported a predominant panhandle structure and did not conform to a cloverleaf fold despite the strong evidence for a predicted structure in this conserved region of the viral RNA. Additional viral or cellular factors may be needed to stabilise it into a form with tRNA-like properties

From counting to construction of BPS states in N=4 SYM

We describe a universal element in the group algebra of symmetric groups, whose characters provides the counting of quarter and eighth BPS states at weak coupling in N=4 SYM, refined according to representations of the global symmetry group. A related projector acting on the Hilbert space of the free theory is used to construct the matrix of two-point functions of the states annihilated by the one-loop dilatation operator, at finite N or in the large N limit. The matrix is given simply in terms of Clebsch-Gordan coefficients of symmetric groups and dimensions of U(N) representations. It is expected, by non-renormalization theorems, to contain observables at strong coupling. Using the stringy exclusion principle, we interpret a class of its eigenvalues and eigenvectors in terms of giant gravitons. We also give a formula for the action of the one-loop dilatation operator on the orthogonal basis of the free theory, which is manifestly covariant under the global symmetry.Comment: 41 pages + Appendices, 4 figures; v2 - refs and acknowledgments adde

Biogeochemistry: Early phosphorus redigested

Atmospheric oxygen was maintained at low levels throughout huge swathes of Earth's early history. Estimates of phosphorus availability through time suggest that scavenging from anoxic, iron-rich oceans stabilized this low-oxygen world

Fragmentation of exotic oxygen isotopes

Abrasion-ablation models and the empirical EPAX parametrization of projectile fragmentation are described. Their cross section predictions are compared to recent data of the fragmentation of secondary beams of neutron-rich, unstable 19,20,21O isotopes at beam energies near 600 MeV/nucleon as well as data for stable 17,18O beams

Atomoxetine and Citalopram alter brain network organisation in Parkinson’s disease

Parkinson’s disease has multiple detrimental effects on motor and cognitive systems in the brain. In contrast to motor deficits, cognitive impairments in Parkinson’s disease are usually not ameliorated, and can even be worsened, by dopaminergic treatments. Recent evidence has shown potential benefits from restoring other neurotransmitter deficits, including noradrenergic and serotonergic transmission. Here, we study global and regional brain network organization using task-free imaging (also known as resting-state), which minimizes performance confounds and the bias towards predetermined networks. Thirty-three patients with idiopathic Parkinson’s disease were studied three times in a double-blind, placebo-controlled counter-balanced crossover design, following placebo, 40mg-oral atomoxetine (selective noradrenaline reuptake inhibitor) or 30mg-oral citalopram (selective serotonin reuptake inhibitor). Neuropsychological assessments were performed outside the scanner. Seventy-six controls were scanned without medication to provide normative data for comparison to the patient cohort. Graph theoretical analysis of task-free brain connectivity, with a random 500-node parcellation, was used to measure the effect of disease in placebo-treated state (versus unmedicated controls) and pharmacological intervention (drug versus placebo). Relative to controls, patients on placebo had executive impairments (reduced fluency and inhibitory control), which was reflected in dysfunctional network dynamics in terms of reduced clustering coefficient, hub degree and hub centrality. In patients, atomoxetine improved fluency in proportion to plasma concentration (p=0.006, r2=0.24), and improved response inhibition in proportion to increased hub eigen centrality (p=0.044, r2=0.14). Citalopram did not improve fluency or inhibitory control, but its influence on network integration and efficiency depended on disease severity: clustering (p=0.01, r2=0.22), modularity (p=0.043, r2=0.14) and path length (p=0.006, r2=0.25) increased in patients with milder forms of Parkinson’s disease, but decreased in patients with more advanced disease (UPDRS-III >30). This study supports the use of task-free imaging of brain networks in translational pharmacology of neurodegenerative disorders. We propose that hub connectivity contributes to cognitive performance in Parkinson’s disease, and that noradrenergic treatment strategies can partially restore the neural systems supporting executive function

Application of molecular cytogenetic techniques to clarify apparently balanced complex chromosomal rearrangements in two patients with an abnormal phenotype: case report

<p>Abstract</p> <p>Background</p> <p>Complex chromosomal rearrangements (CCR) are rare cytogenetic findings that are difficult to karyotype by conventional cytogenetic analysis partially because of the relative low resolution of this technique. High resolution genotyping is necessary in order to identify cryptic imbalances, for instance near the multiple breakpoints, to explain the abnormal phenotype in these patients. We applied several molecular techniques to elucidate the complexity of the CCRs of two adult patients with abnormal phenotypes.</p> <p>Results</p> <p>Multicolour fluorescence in situ hybridization (M-FISH) showed that in patient 1 the chromosomes 1, 10, 15 and 18 were involved in the rearrangement whereas for patient 2 the chromosomes 5, 9, 11 and 13 were involved. A 250 k Nsp1 SNP-array analysis uncovered a deletion in chromosome region 10p13 for patient 1, harbouring 17 genes, while patient 2 showed no pathogenic gains or losses. Additional FISH analysis with locus specific BAC-probes was performed, leading to the identification of cryptic interstitial structural rearrangements in both patients.</p> <p>Conclusion</p> <p>Application of M-FISH and SNP-array analysis to apparently balanced CCRs is useful to delineate the complex chromosomal rearrangement in detail. However, it does not always identify cryptic imbalances as an explanation for the abnormal phenotype in patients with a CCR.</p

Deep Molecular Characterization of HIV-1 Dynamics under Suppressive HAART

In order to design strategies for eradication of HIV-1 from infected individuals, detailed insight into the HIV-1 reservoirs that persist in patients on suppressive antiretroviral therapy (ART) is required. In this regard, most studies have focused on integrated (proviral) HIV-1 DNA forms in cells circulating in blood. However, the majority of proviral DNA is replication-defective and archival, and as such, has limited ability to reveal the dynamics of the viral population that persists in patients on suppressive ART. In contrast, extrachromosomal (episomal) viral DNA is labile and as a consequence is a better surrogate for recent infection events and is able to inform on the extent to which residual replication contributes to viral reservoir maintenance. To gain insight into the diversity and compartmentalization of HIV-1 under suppressive ART, we extensively analyzed longitudinal peripheral blood mononuclear cells (PBMC) samples by deep sequencing of episomal and integrated HIV-1 DNA from patients undergoing raltegravir intensification. Reverse-transcriptase genes selectively amplified from episomal and proviral HIV-1 DNA were analyzed by deep sequencing 0, 2, 4, 12, 24 and 48 weeks after raltegravir intensification. We used maximum likelihood phylogenies and statistical tests (AMOVA and Slatkin-Maddison (SM)) in order to determine molecular compartmentalization. We observed low molecular variance (mean variability ≤0.042). Although phylogenies showed that both DNA forms were intermingled within the phylogenetic tree, we found a statistically significant compartmentalization between episomal and proviral DNA samples (P<10−6 AMOVA test; P = 0.001 SM test), suggesting that they belong to different viral populations. In addition, longitudinal analysis of episomal and proviral DNA by phylogeny and AMOVA showed signs of non-chronological temporal compartmentalization (all comparisons P<10−6) suggesting that episomal and proviral DNA forms originated from different anatomical compartments. Collectively, this suggests the presence of a chronic viral reservoir in which there is stochastic release of infectious virus and in which there are limited rounds of de novo infection. This could be explained by the existence of different reservoirs with unique pharmacological accessibility properties, which will require strategies that improve drug penetration/retention within these reservoirs in order to minimise maintenance of the viral reservoir by de novo infection

Cross-Modal Object Recognition Is Viewpoint-Independent

BACKGROUND: Previous research suggests that visual and haptic object recognition are viewpoint-dependent both within- and cross-modally. However, this conclusion may not be generally valid as it was reached using objects oriented along their extended y-axis, resulting in differential surface processing in vision and touch. In the present study, we removed this differential by presenting objects along the z-axis, thus making all object surfaces more equally available to vision and touch. METHODOLOGY/PRINCIPAL FINDINGS: Participants studied previously unfamiliar objects, in groups of four, using either vision or touch. Subsequently, they performed a four-alternative forced-choice object identification task with the studied objects presented in both unrotated and rotated (180 degrees about the x-, y-, and z-axes) orientations. Rotation impaired within-modal recognition accuracy in both vision and touch, but not cross-modal recognition accuracy. Within-modally, visual recognition accuracy was reduced by rotation about the x- and y-axes more than the z-axis, whilst haptic recognition was equally affected by rotation about all three axes. Cross-modal (but not within-modal) accuracy correlated with spatial (but not object) imagery scores. CONCLUSIONS/SIGNIFICANCE: The viewpoint-independence of cross-modal object identification points to its mediation by a high-level abstract representation. The correlation between spatial imagery scores and cross-modal performance suggest that construction of this high-level representation is linked to the ability to perform spatial transformations. Within-modal viewpoint-dependence appears to have a different basis in vision than in touch, possibly due to surface occlusion being important in vision but not touch

Prior Mating Experience Modulates the Dispersal of Drosophila in Males More Than in Females

Cues from both an animal’s internal physiological state and its local environment may influence its decision to disperse. However, identifying and quantifying the causative factors underlying the initiation of dispersal is difficult in uncontrolled natural settings. In this study, we automatically monitored the movement of fruit flies and examined the influence of food availability, sex, and reproductive status on their dispersal between laboratory environments. In general, flies with mating experience behave as if they are hungrier than virgin flies, leaving at a greater rate when food is unavailable and staying longer when it is available. Males dispersed at a higher rate and were more active than females when food was unavailable, but tended to stay longer in environments containing food than did females. We found no significant relationship between weight and activity, suggesting the behavioral differences between males and females are caused by an intrinsic factor relating to the sex of a fly and not simply its body size. Finally, we observed a significant difference between the dispersal of the natural isolate used throughout this study and the widely-used laboratory strain, Canton-S, and show that the difference cannot be explained by allelic differences in the foraging gene