Whole body modelling of musculoskeletal interactions during whole body vibration to inform rehabilitation intervention design

Background: A major secondary complication which can arise in individuals with spinal cord injury (SCI) is disuse-related bone loss as a result of long-term paralysis and immobilisation. An emerging rehabilitation technique used to treat this musculoskeletal degeneration is whole body vibration (WBV). This can be applied to patients in different body positions on a WBV platform in order to stimulate different muscle groups and in turn apply muscle forces to target bones. To treat the disuse-related bone loss, the hypothesis is that WBV intervention can stimulate bone formation indirectly via targeted muscle action, and/or directly if vibration acts as a mechanostimulus on the bone. Aim & Objectives: The aim of this study was to develop whole body computational models of WBV intervention, to inform the design of intervention protocols in SCI patients. Effects of muscle loss were simulated, and activation and forces of different muscles analysed for a number of proposed configurations on the WBV platform. Methods: WBV intervention was simulated using the AnyBody Technology Modelling software by implementing and adapting the currently available standing model. Different body positions (standing, knee flexed standing, squatting) and parameters of WBV such as frequency and amplitude were modelled and analysed, and the muscle actions simulated. Results: Realistic muscle activities compared to the literature were found in all body position configurations without the WBV simulation. When modelling the WBV intervention, only the squatting body position and side-alternating WBV plate were found to give accurate results. The activities of several muscles were recorded in this configuration under a variety of frequencies and amplitudes. Finally muscle forces were analysed with changes in frequency and amplitude and found to cause a corresponding change in the loading of regions the bones of the ilium, tibia, femur, ischium, fibula, sacrum and coccyx. The aim is for the results of this model to be used in the future to inform WBV protocol development for musculoskeletal rehabilitation in SCI and other target patient groups.Background: A major secondary complication which can arise in individuals with spinal cord injury (SCI) is disuse-related bone loss as a result of long-term paralysis and immobilisation. An emerging rehabilitation technique used to treat this musculoskeletal degeneration is whole body vibration (WBV). This can be applied to patients in different body positions on a WBV platform in order to stimulate different muscle groups and in turn apply muscle forces to target bones. To treat the disuse-related bone loss, the hypothesis is that WBV intervention can stimulate bone formation indirectly via targeted muscle action, and/or directly if vibration acts as a mechanostimulus on the bone. Aim & Objectives: The aim of this study was to develop whole body computational models of WBV intervention, to inform the design of intervention protocols in SCI patients. Effects of muscle loss were simulated, and activation and forces of different muscles analysed for a number of proposed configurations on the WBV platform. Methods: WBV intervention was simulated using the AnyBody Technology Modelling software by implementing and adapting the currently available standing model. Different body positions (standing, knee flexed standing, squatting) and parameters of WBV such as frequency and amplitude were modelled and analysed, and the muscle actions simulated. Results: Realistic muscle activities compared to the literature were found in all body position configurations without the WBV simulation. When modelling the WBV intervention, only the squatting body position and side-alternating WBV plate were found to give accurate results. The activities of several muscles were recorded in this configuration under a variety of frequencies and amplitudes. Finally muscle forces were analysed with changes in frequency and amplitude and found to cause a corresponding change in the loading of regions the bones of the ilium, tibia, femur, ischium, fibula, sacrum and coccyx. The aim is for the results of this model to be used in the future to inform WBV protocol development for musculoskeletal rehabilitation in SCI and other target patient groups

Wearable fusion system for assessment of motor function in lesion-symptom mapping studies

Lesion-symptom mapping studies are a critical component of addressing the relationship between brain and behaviour. Recent developments have yielded significant improvements in the imaging and detection of lesion profiles, but the quantification of motor outcomes is still largely performed by subjective and low-resolution standard clinical rating scales. This mismatch means than lesion-symptom mapping studies are limited in scope by scores which lack the necessary accuracy to fully quantify the subcomponents of motor function. The first study conducted aimed to develop a new automated system of motor function which addressed the limitations inherent in the clinical rating scales. A wearable fusion system was designed that included the attachment of inertial sensors to record the kinematics of upper extremity. This was combined with the novel application of mechanomyographic sensors in this field, to enable the quantification of hand/wrist function. Novel outputs were developed for this system which aimed to combine the validity of the clinical rating scales with the high accuracy of measurements possible with a wearable sensor system. This was achieved by the development of a sophisticated classification model which was trained on series of kinematic and myographic measures to classify the clinical rating scale. These classified scores were combined with a series of fine-grained clinical features derived from higher-order sensor metrics. The developed automated system graded the upper-extremity tasks of the Fugl-Meyer Assessment with a mean accuracy of 75\% for gross motor tasks and 66\% for the wrist/hand tasks. This accuracy increased to 85\% and 74\% when distinguishing between healthy and impaired function for each of these tasks. Several clinical features were computed to describe the subcomponents of upper extremity motor function. This fine-grained clinical feature set offers a novel means to complement the low resolution but well-validated standardised clinical rating scales. A second study was performed to utilise the fine-grained clinical feature set calculated in the previous study in a large-scale region-of-interest lesion-symptom mapping study. Statistically significant regions of motor dysfunction were found in the corticospinal tract and the internal capsule, which are consistent with other motor-based lesion-symptom mapping studies. In addition, the cortico-ponto-cerebellar tract was found to be statistically significant when testing with a clinical feature of hand/wrist motor function. This is a novel finding, potentially due to prior studies being limited to quantifying this subcomponent of motor function using standard clinical rating scales. These results indicate the validity and potential of the clinical feature set to provide a more detailed picture of motor dysfunction in lesion-symptom mapping studies.Open Acces

A widespread family of bacterial cell wall assembly proteins

Teichoic acids and acidic capsular polysaccharides are major anionic cell wall polymers (APs) in many bacteria, with various critical cell functions, including maintenance of cell shape and structural integrity, charge and cation homeostasis, and multiple aspects of pathogenesis. We have identified the widespread LytR–Cps2A–Psr (LCP) protein family, of previously unknown function, as novel enzymes required for AP synthesis. Structural and biochemical analysis of several LCP proteins suggest that they carry out the final step of transferring APs from their lipid-linked precursor to cell wall peptidoglycan (PG). In Bacillus subtilis, LCP proteins are found in association with the MreB cytoskeleton, suggesting that MreB proteins coordinate the insertion of the major polymers, PG and AP, into the cell wall

From a consortium sequence to a unified sequence: the Bacillus subtilis 168 reference genome a decade later

Comparative genomics is the cornerstone of identification of gene functions. The immense number of living organisms precludes experimental identification of functions except in a handful of model organisms. The bacterial domain is split into large branches, among which the Firmicutes occupy a considerable space. Bacillus subtilis has been the model of Firmicutes for decades and its genome has been a reference for more than 10 years. Sequencing the genome involved more than 30 laboratories, with different expertises, in a attempt to make the most of the experimental information that could be associated with the sequence. This had the expected drawback that the sequencing expertise was quite varied among the groups involved, especially at a time when sequencing genomes was extremely hard work. The recent development of very efficient, fast and accurate sequencing techniques, in parallel with the development of high-level annotation platforms, motivated the present resequencing work. The updated sequence has been reannotated in agreement with the UniProt protein knowledge base, keeping in perspective the split between the paleome (genes necessary for sustaining and perpetuating life) and the cenome (genes required for occupation of a niche, suggesting here that B. subtilis is an epiphyte). This should permit investigators to make reliable inferences to prepare validation experiments in a variety of domains of bacterial growth and development as well as build up accurate phylogenies

Viral terminal protein directs early organization of phage DNA replication at the bacterial nucleoid

The mechanism leading to protein-primed DNA replication has been studied extensively in vitro. However, little is known about the in vivo organization of the proteins involved in this fundamental process. Here we show that the terminal proteins (TPs) of phages ϕ29 and PRD1, infecting the distantly related bacteria Bacillus subtilis and Escherichia coli, respectively, associate with the host bacterial nucleoid independently of other viral-encoded proteins. Analyses of phage ϕ29 revealed that the TP N-terminal domain (residues 1–73) possesses sequence-independent DNA-binding capacity and is responsible for its nucleoid association. Importantly, we show that in the absence of the TP N-terminal domain the efficiency of ϕ29 DNA replication is severely affected. Moreover, the TP recruits the phage DNA polymerase to the bacterial nucleoid, and both proteins later are redistributed to enlarged helix-like structures in an MreB cytoskeleton-dependent way. These data disclose a key function for the TP in vivo: organizing the early viral DNA replication machinery at the cell nucleoid