Modelling the interaction of small organic molecules with biomacromolecules. III. Interaction of benzoates with anti-p-(p'-azophenylazo)benzoate antibody

A novel approach for modelling the biological activity of organic molecules, which requires simultaneous consideration of the influence of all factors (topological, steric, hydrophobic, and electronic) that determine the bioactivity, is used to study the interaction of a series of benzoates with anti-p-(p'-azophenylazo)benzoate antibody. The results obtained suggest that this biological interaction proceeds by a two-step stereospecific mechanism. The first step requires a geometrical correspondence between the benzoates and the cavity in the biomacromolecule, which enables the pharmacophore to come into close contact with the receptor. The second step is the orbitally controlled electronic interaction between the active parts of the benzoates and the antibody. The electronic interaction results from pi-charge transfer from the pharmacophore to the biomacromolecule and from the formation of pi-complexes. A proposed mathematical model for this biological interaction exhibits some statistical advantages over existing models.     

Do children with focal cerebellar lesions show deficits in shifting attention?

More recent findings suggest a possible role of the cerebellum in nonmotor functions. Disability of individuals with cerebellar damage in rapidly shifting attention is one frequently used example to support cerebellar involvement in mental skills. The original proposal was based on findings in five children with chronic surgical lesions of the cerebellum and a young adult with a degenerative disorder. The aim of the present study was to repeat Akshoomoff and Courchesne's initial findings in a larger group of children with focal cerebellar lesions. Ten children with cerebellar lesions and 10 age- and sex-matched controls were tested. Neocerebellar areas were affected in all children with cerebellar damage except one based on detailed analysis of MRI scans. Subjects had to perform a focus and a shift attention task. Two visual and two auditory stimuli were presented in a pseudorandom order. An ellipse and a high-pitched tone were presented less frequently than a circle and a low-pitched tone. Rare stimuli were presented at five different time intervals. In the focus tasks, subjects had to react to the same rare stimulus of one of the two modalities. In the shift task, subjects had to switch between the two rare stimuli. Motor deficits based on reaction times were small in cerebellar children compared with controls. The ability of target detection did not significantly differ in the children with cerebellar lesions compared with the control children in both the focus and the shift attention task. In particular, children with cerebellar damage showed no significant impairment in rapid (<2 s) shifts of attention. The present findings indicate that the cerebellum may be less critical in attention related processes than suggested previously.     

Postural muscle responses to multidirectional translations in patients with Parkinson's disease

The postural adaptation impairments of patients with Parkinson's disease (PD) suggest that the basal ganglia may be important for quickly modifying muscle activation patterns when the direction of perturbation or stance conditions suddenly change. It is unknown whether their particular instability to backward postural perturbations is due to specific abnormalities of parkinsonian postural muscle synergies in that direction and not present in other directions. In the present study, we test this hypothesis by comparing the patterns of leg and trunk muscle activation in 13 subjects with PD and 13 control subjects in response to eight randomly presented directions of horizontal surface translations while standing with either narrow or wide stance. The direction of maximum activation for each muscle was similar for PD and control subjects, suggesting that the basal ganglia is not critical for programming externally triggered postural synergies. However, antagonist muscle activation was earlier and larger in PD than in control subjects, resulting in coactivation. PD subjects also did not increase the magnitude of muscle activation as much as did control subjects when changing from wide to narrow stance. These results are consistent with the hypothesis that PD results in an inability to shape the pattern and magnitude of postural muscle responses for changes in perturbation direction and in stance position.     

Calculation of extracellular potentials produced by an inclined muscle fibre at a rectangular plate electrode

Generally the anatomy of muscles is rather complex, and the fibres have various inclination angles within the muscles. We suggest a fast and reliable way to calculate extracellular potentials produced at a point or rectangular plate electrode by a muscle fibre of finite length with an arbitrary inclination. A muscle fibre was considered to be a linear timeshift-invariant system of potential generation. Then, similar to the fibre without inclination, the extracellular potential produced by an inclined fibre was represented as the output signal of the system; it was calculated as the convolution of the input signal and impulse response. Irrespective of the inclination, the input signal of the system was the first temporal derivative of the intracellular action potential. The impulse response of the system differed for the fibres with inclination. This required a new method of analytical integration over the rectangular electrode area. The approach provides a chance to simulate and analyze motor unit potentials or F-, H- or M-responses produced by muscles of complicated anatomy (circum-pennate or complex pennate type) at electrodes of actual size and location in normals and patients with neuro-muscular disorders.     

Longitudinal variations of characteristic frequencies of skeletal muscle fibre potentials detected by a bipolar electrode or multi-electrode

We aimed to reveal reasons for longitudinal variations of characteristic frequencies of electromyographic signals detected by surface longitudinal multi-electrodes. Since the terminal phases were reduced in bipolar recordings, wetested whether the frequency variations reflected the effects of the excitation origin and extinction as in monopolar recordings. A precise and fast convolution method to calculate the signals detected by a multielectrode was suggested. The contribution of different electrode poles was introduced in the impulse response. When a longitudinal multi-electrode with an even number of poles was positioned above the end-plate of asymmetrical fibres, the signal mainly reflected the processes of the excitation extinction. This increased the signal mean and median frequencies. Although the effects of origin and extinction of the excitation were significantly reduced in the spatially filtered signals, the frequency variations along the fibre reflected these intrinsic features of any skeletal muscle fibre of finite length.     

Lifetime exposure to self-reported occupational noise and prevalent rheumatoid arthritis in the National Health and Nutrition Examination Survey (2011–2012)

Multiple risk factors for rheumatoid arthritis (RA) have been studied, but there is a dearth of research on occupational noise, which is highly prevalent in the United States (U.S.). This study aimed to determine whether occupational noise exposure was associated with an elevated risk of prevalent RA in the U.S. general population. Data from the 2011 to 2012 cross-sectional, population-based National Health and Nutrition Examination Survey were used for secondary analysis. Self-reported lifetime exposure to very loud noise was linked to self-reported doctor-diagnosed RA in a sample of 4192 participants. Weighted logistic regression was used to obtain nationally representative prevalence odds ratios (OR). The main and fully adjusted models yielded OR = 3.98 (95% CI: 1.74, 9.11) and OR = 2.84 (95% CI: 1.23, 6.57) for participants exposed for ≥ 15 years compared to never exposed participants. Excluding those diagnosed with RA more than five years before the interview, the effect dropped to OR = 3.67 (95% CI: 1.06, 12.75) in the main model, and was no longer significant in the fully adjusted model (OR = 2.68, 95% CI: 0.80, 8.96). The only significant effect modifier was race/ethnicity, with higher risk in Non-Hispanic whites. To conclude, long-term occupational noise exposure might be a modifiable risk factor for RA, but currently, the evidence base is very thin and tenuous.