Deficits in fine motor skills in a genetic animal model of ADHD

<p>Abstract</p> <p>Background</p> <p>In an attempt to model some behavioral aspects of Attention Deficit/Hyperactivity Disorder (ADHD), we examined whether an existing genetic animal model of ADHD is valid for investigating not only locomotor hyperactivity, but also more complex motor coordination problems displayed by the majority of children with ADHD.</p> <p>Methods</p> <p>We subjected young adolescent Spontaneously Hypertensive Rats (SHRs), the most commonly used genetic animal model of ADHD, to a battery of tests for motor activity, gross motor coordination, and skilled reaching. Wistar (WIS) rats were used as controls.</p> <p>Results</p> <p>Similar to children with ADHD, young adolescent SHRs displayed locomotor hyperactivity in a familiar, but not in a novel environment. They also had lower performance scores in a complex skilled reaching task when compared to WIS rats, especially in the most sensitive measure of skilled performance (i.e., single attempt success). In contrast, their gross motor performance on a Rota-Rod test was similar to that of WIS rats.</p> <p>Conclusion</p> <p>The results support the notion that the SHR strain is a useful animal model system to investigate potential molecular mechanisms underlying fine motor skill problems in children with ADHD.</p

ADGRL3 (LPHN3) variants predict substance use disorder

Genetic factors are strongly implicated in the susceptibility to develop externalizing syndromes such as attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder, conduct disorder, and substance use disorder (SUD). Variants in the ADGRL3 (LPHN3) gene predispose to ADHD and predict ADHD severity, disruptive behaviors comorbidity, long-term outcome, and response to treatment. In this study, we investigated whether variants within ADGRL3 are associated with SUD, a disorder that is frequently co-morbid with ADHD. Using family-based, case-control, and longitudinal samples from disparate regions of the world (n = 2698), recruited either for clinical, genetic epidemiological or pharmacogenomic studies of ADHD, we assembled recursive-partitioning frameworks (classification tree analyses) with clinical, demographic, and ADGRL3 genetic information to predict SUD susceptibility. Our results indicate that SUD can be efficiently and robustly predicted in ADHD participants. The genetic models used remained highly efficient in predicting SUD in a large sample of individuals with severe SUD from a psychiatric institution that were not ascertained on the basis of ADHD diagnosis, thus identifying ADGRL3 as a risk gene for SUD. Recursive-partitioning analyses revealed that rs4860437 was the predominant predictive variant. This new methodological approach offers novel insights into higher order predictive interactions and offers a unique opportunity for translational application in the clinical assessment of patients at high risk for SUD

The evolution of antimicrobial peptides in Chiroptera

High viral tolerance coupled with an extraordinary regulation of the immune response makes bats a great model to study host-pathogen evolution. Although many immune-related gene gains and losses have been previously reported in bats, important gene families such as antimicrobial peptides (AMPs) remain understudied. We built an exhaustive bioinformatic pipeline targeting the major gene families of defensins and cathelicidins to explore AMP diversity and analyze their evolution and distribution across six bat families. A combination of manual and automated procedures identified 29 AMP families across queried species, with α-, β-defensins, and cathelicidins representing around 10% of AMP diversity. Gene duplications were inferred in both α-defensins, which were absent in five species, and three β-defensin gene subfamilies, but cathelicidins did not show significant shifts in gene family size and were absent in Anoura caudifer and the pteropodids. Based on lineage-specific gains and losses, we propose diet and diet-related microbiome evolution may determine the evolution of α- and β-defensins gene families and subfamilies. These results highlight the importance of building species-specific libraries for genome annotation in non-model organisms and shed light on possible drivers responsible for the rapid evolution of AMPs. By focusing on these understudied defenses, we provide a robust framework for explaining bat responses to pathogens

Reorganization of Functional Networks in Mild Cognitive Impairment

Whether the balance between integration and segregation of information in the brain is damaged in Mild Cognitive Impairment (MCI) subjects is still a matter of debate. Here we characterize the functional network architecture of MCI subjects by means of complex networks analysis. Magnetoencephalograms (MEG) time series obtained during a memory task were evaluated by synchronization likelihood (SL), to quantify the statistical dependence between MEG signals and to obtain the functional networks. Graphs from MCI subjects show an enhancement of the strength of connections, together with an increase in the outreach parameter, suggesting that memory processing in MCI subjects is associated with higher energy expenditure and a tendency toward random structure, which breaks the balance between integration and segregation. All features are reproduced by an evolutionary network model that simulates the degenerative process of a healthy functional network to that associated with MCI. Due to the high rate of conversion from MCI to Alzheimer Disease (AD), these results show that the analysis of functional networks could be an appropriate tool for the early detection of both MCI and AD

Consortium neuroscience of attention deficit/hyperactivity disorder and autism spectrum disorder:The ENIGMA adventure

International audienc

Brain imaging of the cortex in ADHD: a coordinated analysis of large-scale clinical and population-based samples

Objective: Neuroimaging studies show structural alterations of various brain regions in children and adults with attention deficit hyperactivity disorder (ADHD), although nonreplications are frequent. The authors sought to identify cortical characteristics related to ADHD using large-scale studies. Methods: Cortical thickness and surface area (based on the Desikan–Killiany atlas) were compared between case subjects with ADHD (N=2,246) and control subjects (N=1,934) for children, adolescents, and adults separately in ENIGMA-ADHD, a consortium of 36 centers. To assess familial effects on cortical measures, case subjects, unaffected siblings, and control subjects in the NeuroIMAGE study (N=506) were compared. Associations of the attention scale from the Child Behavior Checklist with cortical measures were determined in a pediatric population sample (Generation-R, N=2,707). Results: In the ENIGMA-ADHD sample, lower surface area values were found in children with ADHD, mainly in frontal, cingulate, and temporal regions; the largest significant effect was for total surface area (Cohen’s d=−0.21). Fusiform gyrus and temporal pole cortical thickness was also lower in children with ADHD. Neither surface area nor thickness differences were found in the adolescent or adult groups. Familial effects were seen for surface area in several regions. In an overlapping set of regions, surface area, but not thickness, was associated with attention problems in the Generation-R sample. Conclusions: Subtle differences in cortical surface area are widespread in children but not adolescents and adults with ADHD, confirming involvement of the frontal cortex and highlighting regions deserving further attention. Notably, the alterations behave like endophenotypes in families and are linked to ADHD symptoms in the population, extending evidence that ADHD behaves as a continuous trait in the population. Future longitudinal studies should clarify individual lifespan trajectories that lead to nonsignificant findings in adolescent and adult groups despite the presence of an ADHD diagnosis

Enhanced production of multi-strange hadrons in high-multiplicity proton-proton collisions

At sufficiently high temperature and energy density, nuclear matter undergoes a transition to a phase in which quarks and gluons are not confined: the quark-gluon plasma (QGP)(1). Such an exotic state of strongly interacting quantum chromodynamics matter is produced in the laboratory in heavy nuclei high-energy collisions, where an enhanced production of strange hadrons is observed(2-6). Strangeness enhancement, originally proposed as a signature of QGP formation in nuclear collisions(7), is more pronounced for multi-strange baryons. Several effects typical of heavy-ion phenomenology have been observed in high-multiplicity proton-proton (pp) collisions(8,9), but the enhanced production of multi-strange particles has not been reported so far. Here we present the first observation of strangeness enhancement in high-multiplicity proton-proton collisions. We find that the integrated yields of strange and multi-strange particles, relative to pions, increases significantly with the event charged-particle multiplicity. The measurements are in remarkable agreement with the p-Pb collision results(10,11), indicating that the phenomenon is related to the final system created in the collision. In high-multiplicity events strangeness production reaches values similar to those observed in Pb-Pb collisions, where a QGP is formed.Peer reviewe

Constraints on jet quenching in p-Pb collisions at root s(NN)=5.02 TeV measured by the event-activity dependence of semi-inclusive hadron-jet distributions

CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFINEP - FINANCIADORA DE ESTUDOS E PROJETOSFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOThe ALICE Collaboration reports the measurement of semi-inclusive distributions of charged-particle jets recoiling from a high-transverse momentum trigger hadron in p-Pb collisions at root s(NN) = 5.02TeV. Jets are reconstructed from charged-particle tracks using the anti-k(T) algorithm with resolution parameter R = 0.2 and 0.4. A data-driven statistical approach is used to correct the uncorrelated background jet yield. Recoil jet distributions are reported for jet transverse momentum 15 < p(T,jet)(ch) < 50 GeV/c and are compared in various intervals of p-Pb event activity, based on charged-particle multiplicity and zero-degree neutral energy in the forward (Pb-going) direction. The semi-inclusive observable is self-normalized and such comparisons do not require the interpretation of p-Pb event activity in terms of collision geometry, in contrast to inclusive jet observables. These measurements provide new constraints on the magnitude of jet quenching in small systems at the LHC. In p-Pb collisions with high event activity, the average medium-induced out-of-cone energy transport for jets with R = 0.4 and 15 < p(T,jet)(ch) < 50 GeV/c is measured to be less than 0.4 GeV/c at 90% confidence, which is over an order of magnitude smaller than a similar measurement for central Pb-Pb collisions at root s(NN) = 2.76 TeV. Comparison is made to theoretical calculations of jet quenching in small systems, and to inclusive jet measurements in p-Pb collisions selected by event activity at the LHC and in d-Au collisions at RHIC.78395113CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFINEP - FINANCIADORA DE ESTUDOS E PROJETOSFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFINEP - FINANCIADORA DE ESTUDOS E PROJETOSFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOSem informaçãoSem informaçãoSem informaçãoAgências de fomento estrangeiras apoiaram essa pesquisa, mais informações acesse artig

Inclusive J/ψ production at forward and backward rapidity in p-Pb collisions at √sNN=8.16 TeV

Inclusive J/psi production is studied in p-Pb interactions at a centre-of-mass energy per nucleon-nucleon collision sqrt(s_NN) = 8.16TeV, using the ALICE detector at the CERN LHC. The J/psi meson is reconstructed, via its decay to a muon pair, in the centre-of-mass rapidity intervals 2.03 < ycms < 3.53 and -4.46 < ycms < -2.96, where positive and negative ycms refer to the p-going and Pb-going direction, respectively. The transverse momentum coverage is pT < 20 GeV/c. In this paper, ycms- and pT-differential cross sections for inclusive J/psi production are presented, and the corresponding nuclear modification factors RpPb are shown. Forward results show a suppression of the J/psi yield with respect to pp collisions, concentrated in the region pT < 5 GeV/c. At backward rapidity no significant suppression is observed. The results are compared to previous measurements by ALICE in p-Pb collisions at sqrt(s_NN) = 5.02TeV and to theoretical calculations. Finally, the ratios RFB between forward- and backward-ycms RpPb values are shown and discussed

Energy dependence and fluctuations of anisotropic flow in Pb-Pb collisions at √sNN=5.02 and 2.76 TeV

Measurements of anisotropic flow coefficients with two- and multi-particle cumulants for inclusive charged particles in Pb-Pb collisions at sqrt(s_NN) = 5.02 and 2.76TeV are reported in the pseudorapidity range |eta|< 0.8 and transverse momentum 0.2 < pT < 50 GeV/c. The full data sample collected by the ALICE detector in 2015 (2010), corresponding to an integrated luminosity of 12.7 (2.0) ub^-1 in the centrality range 0-80%, is analysed. Flow coefficients up to the sixth flow harmonic (v6) are reported and a detailed comparison among results at the two energies is carried out. The pT dependence of anisotropic flow coefficients and its evolution with respect to centrality and harmonic number n are investigated. An approximate power-law scaling of the form vn(pT) ~ pT^(n/3) is observed for all flow harmonics at low pT (0.2 < pT < 3 GeV/c). At the same time, the ratios vn/vm^(n/m) are observed to be essentially independent of pT for most centralities up to about pT = 10 GeV/c. Analysing the differences among higher-order cumulants of elliptic flow (v2), which have different sensitivities to flow fluctuations, a measurement of the standardised skewness of the event-by-event v2 distribution P(v2) is reported and constraints on its higher moments are provided. The Elliptic Power distribution is used to parametrise P(v2), extracting its parameters from fits to cumulants. The measurements are compared to different model predictions in order to discriminate among initial-state models and to constrain the temperature dependence of the shear viscosity to entropy-density ratio