Substance use disorders in adolescents with attention deficit hyperactivity disorder: a 4-year follow-up study

Aim To examine the relationship between a childhood diagnosis of attention deficit hyperactivity disorder (ADHD) with or without oppositional defiant disorder (ODD)/conduct disorder (CD) and the development of later alcohol/drug use disorder [psychoactive substance use disorder (PSUD)] and nicotine dependence in a large European sample of ADHD probands, their siblings and healthy control subjects. Participants design and settingSubjects (n=1017) were participants in the Belgian, Dutch and German part of the International Multicenter ADHD Genetics (IMAGE) study. IMAGE families were identified through ADHD probands aged 5-17 years attending out-patient clinics, and control subjects from the same geographic areas. After a follow-up period (mean: 4.4 years) this subsample was re-assessed at a mean age of 16.4 years. Measurements PSUD and nicotine dependence were assessed using the Diagnostic Interview Schedule for Children, Alcohol Use Disorders Identification Test, Drug Abuse Screening Test and Fagerstrom test for Nicotine Dependence. Findings The ADHD sample was at higher risk of developing PSUD [hazard ratio (HR)=1.77, 95% confidence interval (CI)=1.05-3.00] and nicotine dependence (HR=8.61, 95% CI=2.44-30.34) than healthy controls. The rates of these disorders were highest for ADHD youth who also had CD, but could not be accounted for by this comorbidity. We did not find an increased risk of developing PSUD (HR=1.18, 95% CI=0.62-2.27) or nicotine dependence (HR=1.89, 95% CI=0.46-7.77) among unaffected siblings of ADHD youth. Conclusions A childhood diagnosis of attention deficit hyperactivity disorder is a risk factor for psychoactive substance use disorder and nicotine dependence in adolescence and comorbid conduct disorder, but not oppositional defiant disorder, further increases the risk of developing psychoactive substance use disorder and nicotine dependence

The higher exercise intensity and the presence of allele I of ACE gene elicit a higher post-exercise blood pressure reduction and nitric oxide release in elderly women: an experimental study

<p>Abstract</p> <p>Background</p> <p>The absence of the I allele of the angiotensin converting enzyme (ACE) gene has been associated with higher levels of circulating ACE, lower nitric oxide (NO) release and hypertension. The purposes of this study were to analyze the post-exercise salivary nitrite (NO₂^-) and blood pressure (BP) responses to different exercise intensities in elderly women divided according to their ACE genotype.</p> <p>Methods</p> <p>Participants (n = 30; II/ID = 20 and DD = 10) underwent three experimental sessions: incremental test - IT (15 watts workload increase/3 min) until exhaustion; 20 min exercise 90% anaerobic threshold (90% AT); and 20 min control session without exercise. Volunteers had their BP and NO₂^-measured before and after experimental sessions.</p> <p>Results</p> <p>Despite both intensities showed protective effect on preventing the increase of BP during post-exercise recovery compared to control, post-exercise hypotension and increased NO₂^-release was observed only for carriers of the I allele (p < 0.05).</p> <p>Conclusion</p> <p>Genotypes of the ACE gene may exert a role in post-exercise NO release and BP response.</p

The actin-myosin regulatory MRCK kinases: regulation, biological functions and associations with human cancer

The contractile actin-myosin cytoskeleton provides much of the force required for numerous cellular activities such as motility, adhesion, cytokinesis and changes in morphology. Key elements that respond to various signal pathways are the myosin II regulatory light chains (MLC), which participate in actin-myosin contraction by modulating the ATPase activity and consequent contractile force generation mediated by myosin heavy chain heads. Considerable effort has focussed on the role of MLC kinases, and yet the contributions of the myotonic dystrophy-related Cdc42-binding kinases (MRCK) proteins in MLC phosphorylation and cytoskeleton regulation have not been well characterized. In contrast to the closely related ROCK1 and ROCK2 kinases that are regulated by the RhoA and RhoC GTPases, there is relatively little information about the CDC42-regulated MRCKα, MRCKβ and MRCKγ members of the AGC (PKA, PKG and PKC) kinase family. As well as differences in upstream activation pathways, MRCK and ROCK kinases apparently differ in the way that they spatially regulate MLC phosphorylation, which ultimately affects their influence on the organization and dynamics of the actin-myosin cytoskeleton. In this review, we will summarize the MRCK protein structures, expression patterns, small molecule inhibitors, biological functions and associations with human diseases such as cancer

NMR structure of Hsp12, a protein induced by and required for dietary restriction-induced lifespan extension in yeast.

Dietary restriction (DR) extends lifespan in yeast, worms, flies and mammals, suggesting that it may act via conserved processes. However, the downstream mechanisms by which DR increases lifespan remain unclear. We used a gel based proteomic strategy to identify proteins whose expression was induced by DR in yeast and thus may correlate with longevity. One protein up-regulated by DR was Hsp12, a small heat shock protein induced by various manipulations known to retard ageing. Lifespan extension by growth on 0.5% glucose (DR) was abolished in an hsp12Δ strain, indicating that Hsp12 is essential for the longevity effect of DR. In contrast, deletion of HSP12 had no effect on growth under DR conditions or a variety of environmental stresses, indicating that the effect of Hsp12 on lifespan is not due to increased general stress resistance. Unlike other small heat shock proteins, recombinant Hsp12 displayed negligible in vitro molecular chaperone activity, suggesting that its cellular function does not involve preventing protein aggregation. NMR analysis indicated that Hsp12 is monomeric and intrinsically unfolded in solution, but switches to a 4-helical conformation upon binding to membrane-mimetic SDS micelles. The structure of micelle-bound Hsp12 reported here is consistent with its recently proposed function as a membrane-stabilising 'lipid chaperone'. Taken together, our data suggest that DR-induced Hsp12 expression contributes to lifespan extension, possibly via membrane alterations

Defining language impairments in a subgroup of children with autism spectrum disorder

Autism spectrum disorder (ASD) is diagnosed on the basis of core impairments in pragmatic language skills, which are found across all ages and subtypes. In contrast, there is significant heterogeneity in language phenotypes, ranging from nonverbal to superior linguistic abilities, as defined on standardized tests of vocabulary and grammatical knowledge. The majority of children are verbal but impaired in language, relative to age-matched peers. One hypothesis is that this subgroup has ASD and co-morbid specific language impairment (SLI). An experiment was conducted comparing children with ASD to children with SLI and typically developing controls on aspects of language processing that have been shown to be impaired in children with SLI: repetition of nonsense words. Patterns of performance among the children with ASD and language impairment were similar to those with SLI, and contrasted with the children with ASD and no language impairment and typical controls, providing further evidence for the hypothesis that a subgroup of children with ASD has co-morbid SLI. The findings are discussed in the context of brain imaging studies that have explored the neural bases of language impairment in ASD and SLI, and overlap in the genes associated with elevated risk for these disorders.M01 RR00533 - NCRR NIH HHS; R01 DC10290 - NIDCD NIH HHS; U19 DC03610 - NIDCD NIH HH

Only females in poor condition display a clear preference and prefer males with an average badge

<p>Abstract</p> <p>Background</p> <p>Female condition-dependent variation in mate preference may have important evolutionary implications, not only within the same population but also among populations. There are few experiments, however, on how condition and/or genotype influences female mate preferences. The black throat patch of the male house sparrow, <it>Passer domesticus</it>, is an intensively studied plumage trait. It is often referred to as a 'badge of status' and seems to be involved in female mate choice, but differences exist among populations. Between-population variation in mate preference may occur for condition-dependent mate preferences. We tested the hypothesis that female preference may vary with female quality (body condition). Therefore, we measured female preference for badge size using an aviary two-choice test in which females were presented with two males that had different sizes of badges (enlarged or averaged).</p> <p>Results</p> <p>Overall we did not find a female preference for enlarged or average badges, but low-quality females spent more time near average badge males. Conversely, high-quality females did not show a clear preference.</p> <p>Conclusions</p> <p>Collectively, these results indicate that female preference varies with female quality. Differences in female condition are causes of within-population variation in mating preferences. To our knowledge, our results provide one of the first experimental evidences that variation in preference for a male ornament is associated with female condition. In our study, however, only females of low condition displayed a clear mate preference. Differences observed among populations could be partly explained by differences in female condition.</p

A Three-Dimensional Taxonomy of Achievement Emotions

We present a three-dimensional taxonomy of achievement emotions that considers valence, arousal, and object focus as core features of emotions occurring in achievement settings. By distinguishing between positive and negative emotions (valence), activating and deactivating emotions (arousal), and activity emotions, prospective outcome emotions, and retrospective outcome emotions (object focus), the taxonomy has a 2 × 2 × 3 structure representing 12 groups of achievement emotions. In four studies across different countries (N = 330, 235, 323, and 269 participants in Canada, the US, Germany, and the UK, respectively), we investigated the empirical robustness of the taxonomy in educational (Studies 1-3) and work settings (Study 4). An expanded version of the Achievement Emotions Questionnaire was used to assess 12 key emotions representing the taxonomy. Consistently across the four studies, findings from multilevel facet analysis and structural equation modeling documented the importance of the three dimensions for explaining achievement emotions. In addition, based on hypotheses about relations with external variables, the findings show clear links of the emotions with important antecedents and outcomes. The Big Five personality traits, appraisals of control and value, and context perceptions were predictors of the emotions. The 12 emotions, in turn, were related to participants’ use of strategies, cognitive performance, and self-reported health problems. Taken together, the findings provide robust evidence for the unique positions of different achievement emotions in the proposed taxonomy, as well as unique patterns of relations with external variables. Directions for future research and implications for policy and practice are discussed

Perspectives on the Trypanosoma cruzi-host cell receptor interaction

Chagas disease is caused by the parasite Trypanosoma cruzi. The critical initial event is the interaction of the trypomastigote form of the parasite with host receptors. This review highlights recent observations concerning these interactions. Some of the key receptors considered are those for thromboxane, bradykinin, and for the nerve growth factor TrKA. Other important receptors such as galectin-3, thrombospondin, and laminin are also discussed. Investigation into the molecular biology and cell biology of host receptors for T. cruzi may provide novel therapeutic targets

Spontaneous Reaction Silencing in Metabolic Optimization

Metabolic reactions of single-cell organisms are routinely observed to become dispensable or even incapable of carrying activity under certain circumstances. Yet, the mechanisms as well as the range of conditions and phenotypes associated with this behavior remain very poorly understood. Here we predict computationally and analytically that any organism evolving to maximize growth rate, ATP production, or any other linear function of metabolic fluxes tends to significantly reduce the number of active metabolic reactions compared to typical non-optimal states. The reduced number appears to be constant across the microbial species studied and just slightly larger than the minimum number required for the organism to grow at all. We show that this massive spontaneous reaction silencing is triggered by the irreversibility of a large fraction of the metabolic reactions and propagates through the network as a cascade of inactivity. Our results help explain existing experimental data on intracellular flux measurements and the usage of latent pathways, shedding new light on microbial evolution, robustness, and versatility for the execution of specific biochemical tasks. In particular, the identification of optimal reaction activity provides rigorous ground for an intriguing knockout-based method recently proposed for the synthetic recovery of metabolic function.Comment: 34 pages, 6 figure