Motor patterns of the impaired upper limb in children with unilateral cerebral palsy performing bimanual tasks.

BACKGROUND: Upper limb movement patterns have not yet been identified in bimanual conditions despite the difficulties children with unilateral cerebral palsy have performing bimanual activities. The aim was to identify specific motor patterns from kinematic deviations during bimanual tasks in this population. METHODS: Twenty children with unilateral cerebral palsy and 20 age-matched, typically developing children performed the five tasks of a 3D bimanual protocol. To evaluate upper limb kinematic deviations, 10 Arm Variable Scores were calculated for the affected /non-dominant upper limb of each participant for each task. Sparse K-means cluster analysis was applied to the 50 Arm Variable Scores of all the children to identify motor patterns and determining variables. Clinical tests of impairment (muscle strength, selectivity, spasticity) and function (Assisting hand assessment, Abilhand-Kids) were compared between the clusters obtained. FINDINGS: Three different motor patterns were identified using the data from all the children: mild, proximal-distal and proximal-distal with trunk. The most important cluster determinants were the Arm Variable Scores for pronation-supination and wrist extension. In the cerebral palsy group, scores of impairments (p < .01) and function (Assisting Hand Assessment [p < .001] and Abilhand-Kids [p = .004]) differed for each motor pattern. Supination and wrist extension deviations differed significantly between the groups (p < .001). INTERPRETATION: During performance of bimanual tasks, children with unilateral cerebral palsy used distinct motor patterns that each corresponded to a specific clinical profile. Elbow-wrist deviations were the largest and most decisive and were specific to the cerebral palsy group: they should be the target of interventions to enhance bimanual function. CLINICALTRIALS: gov identifier: NCT03888443.

A new child-friendly 3D bimanual protocol to assess upper limb movement in children with unilateral cerebral palsy: Development and validation.

Unilateral cerebral palsy (uCP) causes upper limb movement disorders that impact on daily activities, especially in bimanual condition. However, a few studies have proposed bimanual tasks for 3D motion analysis. The aim of this study was to validate the new version of a child-friendly, 3D, bimanual protocol for the measurement of joint angles and movement quality variables. Twenty children with uCP and 20 typically developing children (TDC) performed the five-task protocol integrated into a game scenario. Each task specifically targeted one or two upper limb degrees of freedom. Joint angles, smoothness and trajectory straightness were calculated. Elbow extension, supination, wrist extension and adduction amplitudes were reduced; hand trajectories were less smooth and straight in children with uCP compared to TDC. Correlations between the performance-based score and kinematic variables were strong. High within and between-session reliability was found for most joint angle variables and lower reliability was found for smoothness and straightness in most tasks. The results therefore demonstrated the validity and reliability of the new protocol for the objective assessment of bimanual function in children with uCP. The evaluation of both joint angles and movement quality variables should increase understanding of pathological movement patterns and help clinicians to optimize treatment. ClinicalTrials.gov identifier: NCT03888443.

Collision avoidance between two walkers: role-dependent strategies.

This paper studies strategies for collision avoidance between two persons walking along crossing trajectories. It has been previously demonstrated that walkers are able to anticipate the risk of future collision and to react accordingly. The avoidance task has been described as a mutual control of the future distance of closest approach, MPD (i.e., Mininum Predicted Distance). In this paper, we studied the role of each walker in the task of controlling MPD. A specific question was: does the walker giving way (2nd at the crossing) and the one passing first set similar and coordinated strategies? To answer this question, we inspected the effect of motion adaptations on the future distance of closest approach. This analysis is relevant in the case of collision avoidance because subtle anticipatory behaviors or large last moment adaptations can finally yield the same result upon the final crossing distance. Results showed that collision avoidance is performed collaboratively and the crossing order impacts both the contribution and the strategies used: the participant giving way contributes more than the one passing first to avoid the collision. Both walkers reorient their path but the participant giving way also adapts his speed. Future work is planned to investigate the influence of crossing angle and TTC on adaptations as well as new types of interactions, such as intercepting or meeting tasks.

Minimal predicted distance: a common metric for collision avoidance during pairwise interactions between walkers.

This study investigated collision avoidance between two walkers by focusing on the conditions that lead to avoidance manoeuvres in locomotor trajectories. Following the hypothesis of a reciprocal interaction, we suggested a mutual variable as a continuous function of the two walkers' states, denoted minimum predicted distance (MPD). This function predicts the risk of collision, and its evolution over time captures the motion adaptations performed by the walkers. By groups of two, 30 walkers were assigned locomotion tasks which lead to potential collisions. Results showed that walkers adapted their motions only when required, i.e., when MPD is too low (<1 m). We concluded that walkers are able (i) to accurately estimate their reciprocal distance at the time the crossing will occur, and (ii) to mutually adapt this distance. Furthermore, the study of MPD evolution showed three successive phases in the avoidance interaction: observation where MPD(t) is constant, reaction where MPD(t) increases to acceptable values by adapting locomotion and regulation where MPD(t) reaches a plateau and slightly decreases. This final phase demonstrates that collision avoidance is actually performed with anticipation. Future work would consist in inspecting individual motion adaptations and relating them with the variations of MPD.

Can molecular dynamics simulations help in discriminating correct from erroneous protein 3D models?

BACKGROUND: Recent approaches for predicting the three-dimensional (3D) structure of proteins such as de novo or fold recognition methods mostly rely on simplified energy potential functions and a reduced representation of the polypeptide chain. These simplifications facilitate the exploration of the protein conformational space but do not permit to capture entirely the subtle relationship that exists between the amino acid sequence and its native structure. It has been proposed that physics-based energy functions together with techniques for sampling the conformational space, e.g., Monte Carlo or molecular dynamics (MD) simulations, are better suited to the task of modelling proteins at higher resolutions than those of models obtained with the former type of methods. In this study we monitor different protein structural properties along MD trajectories to discriminate correct from erroneous models. These models are based on the sequence-structure alignments provided by our fold recognition method, FROST. We define correct models as being built from alignments of sequences with structures similar to their native structures and erroneous models from alignments of sequences with structures unrelated to their native structures. RESULTS: For three test sequences whose native structures belong to the all-alpha, all-beta and alphabeta classes we built a set of models intended to cover the whole spectrum: from a perfect model, i.e., the native structure, to a very poor model, i.e., a random alignment of the test sequence with a structure belonging to another structural class, including several intermediate models based on fold recognition alignments. We submitted these models to 11 ns of MD simulations at three different temperatures. We monitored along the corresponding trajectories the mean of the Root-Mean-Square deviations (RMSd) with respect to the initial conformation, the RMSd fluctuations, the number of conformation clusters, the evolution of secondary structures and the surface area of residues. None of these criteria alone is 100% efficient in discriminating correct from erroneous models. The mean RMSd, RMSd fluctuations, secondary structure and clustering of conformations show some false positives whereas the residue surface area criterion shows false negatives. However if we consider these criteria in combination it is straightforward to discriminate the two types of models. CONCLUSION: The ability of discriminating correct from erroneous models allows us to improve the specificity and sensitivity of our fold recognition method for a number of ambiguous cases.

Protein secondary structure assignment revisited: a detailed analysis of different assignment methods.

BACKGROUND: A number of methods are now available to perform automatic assignment of periodic secondary structures from atomic coordinates, based on different characteristics of the secondary structures. In general these methods exhibit a broad consensus as to the location of most helix and strand core segments in protein structures. However the termini of the segments are often ill-defined and it is difficult to decide unambiguously which residues at the edge of the segments have to be included. In addition, there is a "twilight zone" where secondary structure segments depart significantly from the idealized models of Pauling and Corey. For these segments, one has to decide whether the observed structural variations are merely distorsions or whether they constitute a break in the secondary structure. METHODS: To address these problems, we have developed a method for secondary structure assignment, called KAKSI. Assignments made by KAKSI are compared with assignments given by DSSP, STRIDE, XTLSSTR, PSEA and SECSTR, as well as secondary structures found in PDB files, on 4 datasets (X-ray structures with different resolution range, NMR structures). RESULTS: A detailed comparison of KAKSI assignments with those of STRIDE and PSEA reveals that KAKSI assigns slightly longer helices and strands than STRIDE in case of one-to-one correspondence between the segments. However, KAKSI tends also to favor the assignment of several short helices when STRIDE and PSEA assign longer, kinked, helices. Helices assigned by KAKSI have geometrical characteristics close to those described in the PDB. They are more linear than helices assigned by other methods. The same tendency to split long segments is observed for strands, although less systematically. We present a number of cases of secondary structure assignments that illustrate this behavior. CONCLUSION: Our method provides valuable assignments which favor the regularity of secondary structure segments.

From NMR chemical shifts to amino acid types: investigation of the predictive power carried by nuclei.

An approach to automatic prediction of the amino acid type from NMR chemical shift values of its nuclei is presented here, in the frame of a model to calculate the probability of an amino acid type given the set of chemical shifts. The method relies on systematic use of all chemical shift values contained in the BioMagResBank (BMRB). Two programs were designed, one (BMRB stats) for extracting statistical chemical shift parameters from the BMRB and another one (RESCUE2) for computing the probabilities of each amino acid type, given a set of chemical shifts. The Bayesian prediction scheme presented here is compared to other methods already proposed: PROTYP RESCUE and PLATON and is found to be more sensitive and more specific. Using this scheme, we tested various sets of nuclei. The two nuclei carrying the most information are C(beta) and H(beta), in agreement with observations made in Grzesiek and Bax, 1993. Based on four nuclei: H(beta), C(beta), C(alpha) and C', it is possible to increase correct predictions to a rate of more than 75%. Taking into account the correlations between the nuclei chemical shifts has only a slight impact on the percentage of correct predictions: indeed, the largest correlation coefficients display similar features on all amino acids.

Molecular cloning and characterization of an endo-1,3-beta-D-glucanase from the mollusk Spisula sachalinensis.

cDNA encoding the endo-1,3-beta-d-glucanase from Spisula sachalinensis (LIV) was amplified by PCR using oligonucleotides deduced from the N-terminal end peptide sequence. Predicted enzyme structure consists of 444 amino acids with a signal sequence. The mature enzyme has 316 amino acids and its deduced amino acid sequence coincides completely with the N-terminal end (38 amino acids) of the beta-1,3-glucanase (LIV) isolated from the mollusk. The enzyme sequence from Val 121 to Met 441 reveals closest homology with Pacifastacus leniusculus lipopolysaccharide- and beta-1,3-glucan-binding protein and with coelomic cytolytic factors from Lumbricus terrestris. The mollusk glucanase also shows 36% identity and 56% similarity with beta-1,3-glucanase of the sea urchin Strongylocentrotus purpuratus. It is generally considered that invertebrate glucanase-like proteins containing the bacterial glucanase motif have evolved from an ancient beta-1,3-glucanase gene, but most of them lost their glucanase activity in the course of evolution and retained only the glucan-binding activity. A more detailed evaluation of the protein folding elicited very interesting relationships between the active site of LIV and other enzymes, which hydrolyze native glucans.

A Novel H-NS-like protein from an antarctic psychrophilic bacterium reveals a crucial role for the N-terminal domain in thermal stability.

We describe here new members of the H-NS protein family identified in a psychrotrophic Acinetobacter spp. bacterium collected in Siberia and in a psychrophilic Psychrobacter spp. bacterium collected in Antarctica. Both are phylogenetically closely related to the HvrA and SPB Rhodobacter transcriptional regulators. Their amino acid sequence shares 40% identity, and their predicted secondary structure displays a structural and functional organization in two modules similar to that of H-NS in Escherichia coli. Remarkably, the Acinetobacter protein fully restores to the wild-type H-NS-dependent phenotypes, whereas the Psychrobacter protein is no longer able to reverse the effects of H-NS deficiency in an E. coli mutant strain above 30 degrees C. Moreover, in vitro experiments demonstrate that the ability of the Psychrobacter H-NS protein to bind curved DNA and to form dimers is altered at 37 degrees C. The construction of hybrid proteins containing the N- or the C-terminal part of E. coli H-NS fused to the C- or N-terminal part of the Psychrobacter protein demonstrates the role of the N-terminal domain in this process. Finally, circular dichroism analysis of purified H-NS proteins suggests that, as compared with the E. coli and Acinetobacter proteins, the alpha-helical domain displays weaker intermolecular interactions in the Psychrobacter protein, which may account for the low thermal stability observed at 37 degrees C.

Homology modeling and molecular dynamics simulations of the N-terminal domain of wheat high molecular weight glutenin subunit 10.

High molecular weight glutenin subunits (HMW-GS) are of a particular interest because of their biomechanical properties, which are important in many food systems such as breadmaking. Using fold-recognition techniques, we identified a fold compatible with the N-terminal domain of HMW-GS Dy10. This fold corresponds to the one adopted by proteins belonging to the cereal inhibitor family. Starting from three known protein structures of this family as templates, we built three models for the N-terminal domain of HMW-GS Dy10. We analyzed these models, and we propose a number of hypotheses regarding the N-terminal domain properties that can be tested experimentally. In particular, we discuss two possible ways of interaction between the N-terminal domains of the y-type HMW glutenin subunits. The first way consists in the creation of interchain disulfide bridges. According to our models, we propose two plausible scenarios: (1) the existence of an intrachain disulfide bridge between cysteines 22 and 44, leaving the three other cysteines free of engaging in intermolecular bonds; and (2) the creation of two intrachain disulfide bridges (involving cysteines 22-44 and cysteines 10-55), leaving a single cysteine (45) for creating an intermolecular disulfide bridge. We discuss these scenarios in relation to contradictory experimental results. The second way, although less likely, is nevertheless worth considering. There might exist a possibility for the N-terminal domain of Dy10, Nt-Dy10, to create oligomers, because homologous cereal inhibitor proteins are known to exist as monomers, homodimers, and heterooligomers. We also discuss, in relation to the function of the cereal inhibitor proteins, the possibility that this N-terminal domain has retained similar inhibitory functions.

FROST: a filter-based fold recognition method.

To assess the reliability of fold assignments to protein sequences, we developed a fold recognition method called FROST (Fold Recognition-Oriented Search Tool) based on a series of filters and a database specifically designed as a benchmark for this new method under realistic conditions. This benchmark database consists of proteins for which there exists, at least, another protein with an extensively similar 3D structure in a database of representative 3D structures (i.e., more than 65% of the residues in both proteins can be structurally aligned). Because the testing of our method must be carried out under conditions similar to those of real fold recognition experiments, no protein pair with sequence similarity detectable using standard sequence comparison methods such as FASTA is included in the benchmark database. While using FROST, we achieved a coverage of 60% for a rate of error of 1%. To obtain a baseline for our method, we used PSI-BLAST and 3D-PSSM. Under the same conditions, for a 1% error rate, coverages for PSI-BLAST and 3D-PSSM were 33 and 56%, respectively.