Interference control in children with attention deficit/hyperactivity disorder

The view that Attention Deficit/Hyperactivity Disorder (ADHD) is associated with a diminished ability to control interfference is controversial and based exclusively on results of (verbal)-visual interference tasks, primarily the Stroop Color Word task. The present study compares medication-naïve children with ADHD (n∈=∈35 and n∈=∈51 in Experiments 1 and 2, respectively) with normal controls (n∈=∈26 and n∈=∈32, respectively) on two interference tasks to assess interference control in both the auditory and the visual modality: an Auditory Stroop task and a Simon task. Both groups showed reliable but equal degrees of interference on both tasks, suggesting that children with ADHD do not differ from normal controls in their ability to control interference in either modality. © 2008 The Author(s)

Inhibition, Reinforcement Sensitivity and Temporal Information Processing in ADHD and ADHD+ODD: Evidence of a Separate Entity?

This study compared children with ADHD-only, ADHD+ODD and normal controls (age 8–12) on three key neurocognitive functions: response inhibition, reinforcement sensitivity, and temporal information processing. The goal was twofold: (a) to investigate neurocognitive impairments in children with ADHD-only and children with ADHD+ODD, and (b) to test whether ADHD+ODD is a more severe from of ADHD in terms of neurocognitive performance. In Experiment 1, inhibition abilities were measured using the Stop Task. In Experiment 2, reinforcement sensitivity and temporal information processing abilities were measured using a Timing Task with both a reward and penalty condition. Compared to controls, children with ADHD-only demonstrated impaired inhibitory control, showed more time underestimations, and showed performance deterioration in the face of reward and penalty. Children with ADHD+ODD performed in-between children with ADHD-only and controls in terms of inhibitory controls and the tendency to underestimate time, but were more impaired than controls and children with ADHD-only in terms of timing variability. In the face of reward and penalty children with ADHD+ODD improved their performance compared to a neutral condition, in contrast to children with ADHD-only. In the face of reward, the performance improvement in the ADHD+ODD group was disproportionally larger than that of controls. Taken together the findings suggest that, in terms of neurocognitive functioning, comorbid ADHD+ODD is a substantial different entity than ADHD-only

Investigating Homology between Proteins using Energetic Profiles

Accumulated experimental observations demonstrate that protein stability is often preserved upon conservative point mutation. In contrast, less is known about the effects of large sequence or structure changes on the stability of a particular fold. Almost completely unknown is the degree to which stability of different regions of a protein is generally preserved throughout evolution. In this work, these questions are addressed through thermodynamic analysis of a large representative sample of protein fold space based on remote, yet accepted, homology. More than 3,000 proteins were computationally analyzed using the structural-thermodynamic algorithm COREX/BEST. Estimated position-specific stability (i.e., local Gibbs free energy of folding) and its component enthalpy and entropy were quantitatively compared between all proteins in the sample according to all-vs.-all pairwise structural alignment. It was discovered that the local stabilities of homologous pairs were significantly more correlated than those of non-homologous pairs, indicating that local stability was indeed generally conserved throughout evolution. However, the position-specific enthalpy and entropy underlying stability were less correlated, suggesting that the overall regional stability of a protein was more important than the thermodynamic mechanism utilized to achieve that stability. Finally, two different types of statistically exceptional evolutionary structure-thermodynamic relationships were noted. First, many homologous proteins contained regions of similar thermodynamics despite localized structure change, suggesting a thermodynamic mechanism enabling evolutionary fold change. Second, some homologous proteins with extremely similar structures nonetheless exhibited different local stabilities, a phenomenon previously observed experimentally in this laboratory. These two observations, in conjunction with the principal conclusion that homologous proteins generally conserved local stability, may provide guidance for a future thermodynamically informed classification of protein homology

SecA, a remarkable nanomachine

Biological cells harbor a variety of molecular machines that carry out mechanical work at the nanoscale. One of these nanomachines is the bacterial motor protein SecA which translocates secretory proteins through the protein-conducting membrane channel SecYEG. SecA converts chemically stored energy in the form of ATP into a mechanical force to drive polypeptide transport through SecYEG and across the cytoplasmic membrane. In order to accommodate a translocating polypeptide chain and to release transmembrane segments of membrane proteins into the lipid bilayer, SecYEG needs to open its central channel and the lateral gate. Recent crystal structures provide a detailed insight into the rearrangements required for channel opening. Here, we review our current understanding of the mode of operation of the SecA motor protein in concert with the dynamic SecYEG channel. We conclude with a new model for SecA-mediated protein translocation that unifies previous conflicting data

The Unique and Combined Effects of Reinforcement and Methylphenidate on Temporal Information Processing in Attention-Deficit/Hyperactivity Disorder (ADHD)

Temporal information processing and reward sensitivity are neurocognitive impairments key to attention-deficit/hyperactivity disorder (ADHD). The aim of this study was to examine the unique and combined impact of reinforcement and methylphenidate (MPH) on temporal information processing in children with ADHD. We predicted that both monetary reinforcement and MPH would ameliorate temporal information processing deficits in ADHD, and we expected that the combined effect of reinforcement and MPH would be most beneficial. Forty children (23 with ADHD and 27 typical controls, aged 8-12 y) performed a time production task under 3 conditions: reward, response cost, and feedback only. Children with ADHD also performed the task (in random order) with placebo, a low, a medium, and a high dose of MPH. Dependent variables were time production accuracy and variability. At baseline, children with ADHD displayed poor internal clock functioning compared with controls, as reflected by greater underestimations of the 1-second interval, and they showed poor motor output as reflected by increased timing variability. Reward and response cost improved motor output (timing variability), with similar effects for both groups. Methylphenidate increased performance (timing variability) compared with placebo, with a higher dose showing greater effects. Effect sizes of reinforcement and medication were medium to large. Contrary to expectations, MPH did not add to the reinforcement effect. The results of this study confirm the value of reward and response cost being similar to that of MPH to optimize (timing) performance of children with ADH