This article examines the effect of a bout of unloaded leg cycling on the soleus H-reflex and modified Ashworth scale (MAS) in 6 individuals with multiple sclerosis (MS) who had spasticity of the leg muscles and were currently taking anti-spastic medications. H-reflex and MAS data were collected bef

This article examines the effect of a bout of unloaded leg cycling on the soleus H-reflex and modified Ashworth scale (MAS) in 6 individuals with multiple sclerosis (MS) who had spasticity of the leg muscles and were currently taking anti-spastic medications. H-reflex and MAS data were collected before and 10, 30, and 60 min after 20 min of unloaded leg cycling and a control condition. The unloaded leg cycling resulted in concomitant reductions in soleus H-reflex and MAS scores compared with the control condition. This provides a basis for incorporating exercise along with anti-spastic medications into a multifaceted plan for spasticity management in individuals with MS.

The aim of this study was to examine the effects of transcutaneous electrical nerve stimulation on spasticity in patients with multiple sclerosis. The study was carried out in the Hacettepe University School of Physical Therapy and Rehabilitation. The subjects in the study were 10 clinically definit

The aim of this study was to examine the effects of transcutaneous electrical nerve stimulation on spasticity in patients with multiple sclerosis. The study was carried out in the Hacettepe University School of Physical Therapy and Rehabilitation. The subjects in the study were 10 clinically definite, primary and secondary progressive type multiple sclerosis outpatients with mild to moderate spasticity in the plantar flexor muscles of the ankle. Stimuli of frequency 100 Hz and pulse width 0.3 msec were used 20 minutes per day for 4 weeks. Patients were assessed by electromyography, Modified Ashworth Scale, and Ambulation Index. Electromyography was performed before and after the daily treatment of spastic muscles with transcutaneous electrical nerve stimulation in order to assess the effect on muscle relaxation. The Modified Ashworth Scale and Ambulation Index were used before and after 4 weeks' treatment. After 4 weeks of treatment, there were statistically significant reductions in spasticity of both extremities as assessed by myoelectric activity and the Modified Ashworth Scale (P < 0.05). Ambulation Index level was not improved significantly (P > 0.05).

We report on a multiple sclerosis patient who received functional electrical stimulation to reduce spastic muscle tone of the lower limbs. Stimulation by means of surface electrodes applied to the thigh muscles induced cycling leg movements. Spastic muscle tone was measured clinically using the modi

We report on a multiple sclerosis patient who received functional electrical stimulation to reduce spastic muscle tone of the lower limbs. Stimulation by means of surface electrodes applied to the thigh muscles induced cycling leg movements. Spastic muscle tone was measured clinically using the modified Ashworth scale and semiautomatically by pendulum testing of spasticity. This was done before and directly after stimulation. The patient was able to endure the stimulation for ca. 30 minutes; there was a significant reduction of spasticity after each stimulation session. We conclude, that this type of stimulation could be another potential treatment modality for multiple sclerosis patients, especially those with a high score in the expanded disability Status scale.

OBJECTIVE: Functional electrical stimulation (FES) is used clinically in the management of drop foot in people suffering from neurological conditions. The aim of the study was to investigate the effects of FES, in terms of speed and physiological cost of gait, in people with multiple sclerosis (pwMS

OBJECTIVE: Functional electrical stimulation (FES) is used clinically in the management of drop foot in people suffering from neurological conditions. The aim of the study was to investigate the effects of FES, in terms of speed and physiological cost of gait, in people with multiple sclerosis (pwMS). METHODS: Twelve pwMS and 12 healthy matched controls walked at their own preferred walking speed (PWS) for 5 min around a 10 m elliptical course. Subjects with MS completed the protocol with and without using their FES. In addition, control subjects completed the protocol twice more walking at the same PWS of the pwMS to which they were matched. RESULTS: Wearing FES lead to a significant improvement in walking speed (0.49 ms(-1) and 0.43 ms(-1) with and without their FES respectively; P<0.001) and a significant reduction in the physiological cost of gait (0.41 mL min(-1) kg(-1) m(-1) and 0.46 mL min(-1) kg(-1) m(-1) with and without FES respectively; P=0.017) in pwMS. The speed of walking, oxygen uptake, and physiological cost were significantly different between pwMS and controls both at preferred and matched speeds. Although pwMS exhibit a higher physiological cost of walking, FES offers an orthotic benefit to pwMS and should be considered as a possible treatment option.

Small deviations from the expected relative positions of multiplet components in double- and zero-quantum 1H-13C methyl correlation maps have been observed in spectra recorded on a 7-kDa protein. These dynamic frequency shifts (DFS) are the result of dipolar cross-correlations that derive from field

Small deviations from the expected relative positions of multiplet components in double- and zero-quantum 1H-13C methyl correlation maps have been observed in spectra recorded on a 7-kDa protein. These dynamic frequency shifts (DFS) are the result of dipolar cross-correlations that derive from fields produced by the spins within the methyl groups. The shifts have been quantified and compared with values calculated from a Redfield analysis. Good agreement is noted between the signs of the predicted and experimentally observed relative shifts of lines in both F1 and F2 dimensions of spectra, as well as between the magnitudes of the calculated and observed shifts in the F2 (1H) dimension. The experimental DFS values show a reasonable correlation with 2H relaxation-derived measures of methyl side-chain dynamics, as expected from theory. This suggests that in cases where such shifts can be quantified, they can serve as qualitative measures of motion.

BACKGROUND: Cis-regulatory modules are combinations of regulatory elements occurring in close proximity to each other that control the spatial and temporal expression of genes. The ability to identify them in a genome-wide manner depends on the availability of accurate models and of search methods a

BACKGROUND: Cis-regulatory modules are combinations of regulatory elements occurring in close proximity to each other that control the spatial and temporal expression of genes. The ability to identify them in a genome-wide manner depends on the availability of accurate models and of search methods able to detect putative regulatory elements with enhanced sensitivity and specificity. RESULTS: We describe the implementation of a search method for putative transcription factor binding sites (TFBSs) based on hidden Markov models built from alignments of known sites. We built 1,079 models of TFBSs using experimentally determined sequence alignments of sites provided by the TRANSFAC and JASPAR databases and used them to scan sequences of the human, mouse, fly, worm and yeast genomes. In several cases tested the method identified correctly experimentally characterized sites, with better specificity and sensitivity than other similar computational methods. Moreover, a large-scale comparison using synthetic data showed that in the majority of cases our method performed significantly better than a nucleotide weight matrix-based method. CONCLUSION: The search engine, available at http://mapper.chip.org, allows the identification, visualization and selection of putative TFBSs occurring in the promoter or other regions of a gene from the human, mouse, fly, worm and yeast genomes. In addition it allows the user to upload a sequence to query and to build a model by supplying a multiple sequence alignment of binding sites for a transcription factor of interest. Due to its extensive database of models, powerful search engine and flexible interface, MAPPER represents an effective resource for the large-scale computational analysis of transcriptional regulation.

We have developed a web server for the life sciences community to use to search for short repeats of DNA sequence of length between 3 and 10,000 bases within multiple species. This search employs a unique and fast hash function approach. Our system also applies information retrieval algorithms to di

We have developed a web server for the life sciences community to use to search for short repeats of DNA sequence of length between 3 and 10,000 bases within multiple species. This search employs a unique and fast hash function approach. Our system also applies information retrieval algorithms to discover knowledge of cross-species conservation of repeat sequences. Furthermore, we have incorporated a part of the Gene Ontology database into our information retrieval algorithms to broaden the coverage of the search. Our web server and tutorial can be found at http://acmes.rnet.missouri.edu.

The unfolding pathways of multiple-repeat spectrin molecules were examined using steered molecular dynamics (SMD) simulations to forcibly unfold double- and triple-repeat spectrin molecules. Although SMD has previously been used to study other repeating-domain proteins, spectrin offers a unique chal

The unfolding pathways of multiple-repeat spectrin molecules were examined using steered molecular dynamics (SMD) simulations to forcibly unfold double- and triple-repeat spectrin molecules. Although SMD has previously been used to study other repeating-domain proteins, spectrin offers a unique challenge in that the linker connecting repeat units has a definite secondary structure, that of an alpha-helix. Therefore, the boundary conditions imposed on a double- or triple-repeat spectrin must be carefully considered if any relationship to the real system is to be deduced. This was accomplished by imposing additional forces on the system which ensure that the terminal alpha-helices behave as if there were no free noncontiguous helical ends. The results of the SMD simulations highlight the importance of the rupture of the alpha-helical linker on the subsequent unfolding events. Rupture of the linker propagates unfolding in the adjacent repeat units by destabilizing the tertiary structure, ultimately resulting in complete unfolding of the affected repeat unit. Two dominant classes of unfolding pathways are observed after the initial rupture of a linker which involve either rupture of another linker (possibly adjacent) or rupture of the basic tertiary structure of a repeat unit. The relationship between the force response observed on simulation timescales and those of experiment or physiological conditions is also discussed.

The ff94 force field that is commonly associated with the Amber simulation package is one of the most widely used parameter sets for biomolecular simulation. After a decade of extensive use and testing, limitations in this force field, such as over-stabilization of alpha-helices, were reported by us

The ff94 force field that is commonly associated with the Amber simulation package is one of the most widely used parameter sets for biomolecular simulation. After a decade of extensive use and testing, limitations in this force field, such as over-stabilization of alpha-helices, were reported by us and other researchers. This led to a number of attempts to improve these parameters, resulting in a variety of "Amber" force fields and significant difficulty in determining which should be used for a particular application. We show that several of these continue to suffer from inadequate balance between different secondary structure elements. In addition, the approach used in most of these studies neglected to account for the existence in Amber of two sets of backbone phi/psi dihedral terms. This led to parameter sets that provide unreasonable conformational preferences for glycine. We report here an effort to improve the phi/psi dihedral terms in the ff99 energy function. Dihedral term parameters are based on fitting the energies of multiple conformations of glycine and alanine tetrapeptides from high level ab initio quantum mechanical calculations. The new parameters for backbone dihedrals replace those in the existing ff99 force field. This parameter set, which we denote ff99SB, achieves a better balance of secondary structure elements as judged by improved distribution of backbone dihedrals for glycine and alanine with respect to PDB survey data. It also accomplishes improved agreement with published experimental data for conformational preferences of short alanine peptides and better accord with experimental NMR relaxation data of test protein systems.

Multiple sequence alignment is perhaps the most commonly applied bioinformatics technique. It often leads to fundamental biological insight into sequence-structure-function relationships of nucleotide or protein sequence families. In this unit, an overview of multiple sequence alignment techniques i

Multiple sequence alignment is perhaps the most commonly applied bioinformatics technique. It often leads to fundamental biological insight into sequence-structure-function relationships of nucleotide or protein sequence families. In this unit, an overview of multiple sequence alignment techniques is presented, covering a history of nearly 30 years from the early pioneering methods to the current state-of-the-art techniques. Methodological and biological issues and end-user considerations, as well as alignment evaluation issues, are discussed.