Effect of Gait Imagery Tasks on Lower Limb Muscle Activity With Respect to Body Posture

The objective of this study was to evaluate the effect of gait imagery tasks on lowerlimb muscle activity with respect to body posture. The sitting and standing position and lower limb muscle activity were evaluated in 27 healthy female students (24.4±1.3 years, 167.2±5.2 cm, 60.10±6.4 kg). Surface electromyography was assessed during rest and in three different experimental conditions using mental imagery. These included a rhythmic gait, rhythmic gait simultaneously with observation of a model, and rhythmic gait after performing rhythmic gait. The normalized root mean square EMG values with respect to corresponding rest position were compared using non-parametric statistics. Standing gait imagery tasks had facilitatory effect on proximal lower limb muscle activity. However, electromyography activity of distal leg muscles decreased for all gait imagery tasks in the sitting position, when the proprioceptive feedback was less appropriate. For subsequent gait motor imagery tasks, the muscle activity decreased, probably as result of habituation. In conclusion, the effect of motor imagery on muscle activity appears to depend on relative strength of facilitatory and inhibitory inputs

High-performance liquid chromatography–tandem mass spectrometry in the identification and determination of phase I and phase II drug metabolites

Applications of tandem mass spectrometry (MS/MS) techniques coupled with high-performance liquid chromatography (HPLC) in the identification and determination of phase I and phase II drug metabolites are reviewed with an emphasis on recent papers published predominantly within the last 6 years (2002–2007) reporting the employment of atmospheric pressure ionization techniques as the most promising approach for a sensitive detection, positive identification and quantitation of metabolites in complex biological matrices. This review is devoted to in vitro and in vivo drug biotransformation in humans and animals. The first step preceding an HPLC-MS bioanalysis consists in the choice of suitable sample preparation procedures (biomatrix sampling, homogenization, internal standard addition, deproteination, centrifugation, extraction). The subsequent step is the right optimization of chromatographic conditions providing the required separation selectivity, analysis time and also good compatibility with the MS detection. This is usually not accessible without the employment of the parent drug and synthesized or isolated chemical standards of expected phase I and sometimes also phase II metabolites. The incorporation of additional detectors (photodiode-array UV, fluorescence, polarimetric and others) between the HPLC and MS instruments can result in valuable analytical information supplementing MS results. The relation among the structural changes caused by metabolic reactions and corresponding shifts in the retention behavior in reversed-phase systems is discussed as supporting information for identification of the metabolite. The first and basic step in the interpretation of mass spectra is always the molecular weight (MW) determination based on the presence of protonated molecules [M+H]+ and sometimes adducts with ammonium or alkali-metal ions, observed in the positive-ion full-scan mass spectra. The MW determination can be confirmed by the [M-H]- ion for metabolites providing a signal in negative-ion mass spectra. MS/MS is a worthy tool for further structural characterization because of the occurrence of characteristic fragment ions, either MSn analysis for studying the fragmentation patterns using trap-based analyzers or high mass accuracy measurements for elemental composition determination using time of flight based or Fourier transform mass analyzers. The correlation between typical functional groups found in phase I and phase II drug metabolites and corresponding neutral losses is generalized and illustrated for selected examples. The choice of a suitable ionization technique and polarity mode in relation to the metabolite structure is discussed as well

P 025 - Lower limb muscles activity during imagination of gait

Motor imagery (MI) represents a pure cognitive process, which can positively influence motor performance in healthy subjects and in a wide range of patients with movement disorders. Specifically walking ability has been shown to improve after motor imagery exercises. The facilitatory effect of MI on muscle activity has been demonstrated compared to rest conditions for upper limb movements [[1], [2], [3]], however further work is required to consider the effect during lower limb movements

Flexible regions govern promiscuous binding of IL-24 to receptors IL-20R1 and IL-22R1

Interleukin 24 (IL-24) is a cytokine with the potential to be an effective treatment for autoimmune diseases and cancer. However, its instability and difficulties in its production have hampered detailed biological and biophysical studies. We approached the challenges of IL-24 production by using the PROSS algorithm to design more stable variants of IL-24. We used homology models built from the sequences and known structures of IL-20 and IL-19 and predicted and produced several extensively mutated IL-24 variants that were highly stable and produced in large yields; one of them was crystallized (IL-24B, PDB ID 6GG1; 3D Interactive at http://proteopedia.org/w/Journal: FEBS_Journal:1). The mutated variants, however, lost most of their binding capacity to the extracellular parts of cognate receptors. While the affinity to the receptor 2 (IL-20R2) was preserved, the variants lost affinity to IL-20R1 and IL-22R1 (shared receptors 1). Back engineering of the variants revealed that reintroduction of a single IL-24 wild-type residue (T198) to the patch interacting with receptors 1 restored 80% of the binding affinity and signaling capacity, accompanied by an acceptable drop in the protein stability by 9 °C. Multiple sequence alignment explains the stabilizing effect of the mutated residues in the IL-24 variants by their presence in the related and more stable cytokines IL-20 and IL-19. Our homology-based approach can enhance existing methods for protein engineering and represents a viable alternative to study and produce difficult proteins for which only in silico structural information is available, estimated as >40% of all important drug targets