Growth-Rate Dependence Reveals Design Principles of Plasmid Copy Number Control

Genetic circuits in bacteria are intimately coupled to the cellular growth rate as many parameters of gene expression are growth-rate dependent. Growth-rate dependence can be particularly pronounced for genes on plasmids; therefore the native regulatory systems of a plasmid such as its replication control system are characterized by growth-rate dependent parameters and regulator concentrations. This natural growth-rate dependent variation of regulator concentrations can be used for a quantitative analysis of the design of such regulatory systems. Here we analyze the growth-rate dependence of parameters of the copy number control system of ColE1-type plasmids in E. coli. This analysis allows us to infer the form of the control function and suggests that the Rom protein increases the sensitivity of control

Efficacy of motor imagery in post-stroke rehabilitation: a systematic review

BACKGROUND: Evaluation of how Motor Imagery and conventional therapy (physiotherapy or occupational therapy) compare to conventional therapy only in their effects on clinically relevant outcomes during rehabilitation of persons with stroke. DESIGN: Systematic review of the literature METHODS: We conducted an electronic database search in seven databases in August 2005 and also hand-searched the bibliographies of studies that we selected for the review.Two reviewers independently screened and selected all randomized controlled trials that compare the effects of conventional therapy plus Motor Imagery to those of only conventional therapy on stroke patients.The outcome measurements were: Fugl-Meyer Stroke Assessment upper extremity score (66 points) and Action Research Arm Test upper extremity score (57 points).Due to the high variability in the outcomes, we could not pool the data statistically. RESULTS: We identified four randomized controlled trials from Asia and North America. The quality of the included studies was poor to moderate. Two different Motor imagery techniques were used (three studies used audiotapes and one study had occupational therapists apply the intervention). Two studies found significant effects of Motor Imagery in the Fugl-Meyer Stroke Assessment: Differences between groups amounted to 11.0 (1.0 to 21.0) and 3.2 (-4 to 10.3) respectively and in the Action Research Arm Test 6.1 (-6.2 to 18.4) and 15.8 (0.5 to 31.0) respectively. One study did not find a significant effect in the Fugl-Meyer Stroke Assessment and Color trail Test (p = 0.28) but in the task-related outcomes (p > 0.001). CONCLUSION: Current evidence suggests that Motor imagery provides additional benefits to conventional physiotherapy or occupational therapy. However, larger and methodologically sounder studies should be conducted to assess the benefits of Motor imagery

Increasing upper limb training intensity in chronic stroke using embodied virtual reality: a pilot study.

Technology-mediated neurorehabilitation is suggested to enhance training intensity and therefore functional gains. Here, we used a novel virtual reality (VR) system for task-specific upper extremity training after stroke. The system offers interactive exercises integrating motor priming techniques and embodied visuomotor feedback. In this pilot study, we examined (i) rehabilitation dose and training intensity, (ii) functional improvements, and (iii) safety and tolerance when exposed to intensive VR rehabilitation. Ten outpatient stroke survivors with chronic (>6 months) upper extremity paresis participated in a ten-session VR-based upper limb rehabilitation program (2 sessions/week). All participants completed all sessions of the treatment. In total, they received a median of 403 min of upper limb therapy, with 290 min of effective training. Within that time, participants performed a median of 4713 goal-directed movements. Importantly, training intensity increased progressively across sessions from 13.2 to 17.3 movements per minute. Clinical measures show that despite being in the chronic phase, where recovery potential is thought to be limited, participants showed a median improvement rate of 5.3% in motor function (Fugl-Meyer Assessment for Upper Extremity; FMA-UE) post intervention compared to baseline, and of 15.4% at one-month follow-up. For three of them, this improvement was clinically significant. A significant improvement in shoulder active range of motion (AROM) was also observed at follow-up. Participants reported very low levels of pain, stress and fatigue following each session of training, indicating that the intensive VR intervention was well tolerated. No severe adverse events were reported. All participants expressed their interest in continuing the intervention at the hospital or even at home, suggesting high levels of adherence and motivation for the provided intervention. This pilot study showed how a dedicated VR system could deliver high rehabilitation doses and, importantly, intensive training in chronic stroke survivors. FMA-UE and AROM results suggest that task-specific VR training may be beneficial for further functional recovery both in the chronic stage of stroke. Longitudinal studies with higher doses and sample sizes are required to confirm the therapy effectiveness. This trial was retrospectively registered at ClinicalTrials.gov database (registration number NCT03094650 ) on 14 March 2017

Brain plasticity following MI-BCI training combined with tDCS in a randomized trial in chronic subcortical stroke subjects: a preliminary study

Brain-computer interface-assisted motor imagery (MI-BCI) or transcranial direct current stimulation (tDCS) has been used in stroke rehabilitation, though their combinatory effect is unknown. We investigated brain plasticity following a combined MI-BCI and tDCS intervention in chronic subcortical stroke patients with unilateral upper limb disability. Nineteen patients were randomized into tDCS and sham-tDCS groups. Diffusion and perfusion MRI, and transcranial magnetic stimulation were used to study structural connectivity, cerebral blood flow (CBF), and corticospinal excitability, respectively, before and 4 weeks after the 2-week intervention. After quality control, thirteen subjects were included in the CBF analysis. Eleven healthy controls underwent 2 sessions of MRI for reproducibility study. Whereas motor performance showed comparable improvement, long-lasting neuroplasticity can only be detected in the tDCS group, where white matter integrity in the ipsilesional corticospinal tract and bilateral corpus callosum was increased but sensorimotor CBF was decreased, particularly in the ipsilesional side. CBF change in the bilateral parietal cortices also correlated with motor function improvement, consistent with the increased white matter integrity in the corpus callosum connecting these regions, suggesting an involvement of interhemispheric interaction. The preliminary results indicate that tDCS may facilitate neuroplasticity and suggest the potential for refining rehabilitation strategies for stroke patients

Functional MRI and Diffusion Tensor Imaging of Brain Reorganization After Experimental Stroke

The potential of the adult brain to reorganize after ischemic injury is critical for functional recovery and provides a significant target for therapeutic strategies to promote brain repair. Despite the accumulating evidence of brain plasticity, the interaction and significance of morphological and physiological modifications in post-stroke brain tissue remain mostly unclear. Neuroimaging techniques such as functional MRI (fMRI) and diffusion tensor imaging (DTI) enable in vivo assessment of the spatial and temporal pattern of functional and structural changes inside and outside ischemic lesion areas. This can contribute to the elucidation of critical aspects in post-stroke brain remodeling. Task/stimulus-related fMRI, resting-state fMRI, or pharmacological MRI enables direct or indirect measurement of neuronal activation, functional connectivity, or neurotransmitter system responses, respectively. DTI allows estimation of the structural integrity and connectivity of white matter tracts. Together, these MRI methods provide an unprecedented means to (a) measure longitudinal changes in tissue structure and function close by and remote from ischemic lesion areas, (b) evaluate the organizational profile of neural networks after stroke, and (c) identify degenerative and restorative processes that affect post-stroke functional outcome. Besides, the availability of MRI in clinical institutions as well as research laboratories provides an optimal basis for translational research on stroke recovery. This review gives an overview of the current status and perspectives of fMRI and DTI applications to study brain reorganization in experimental stroke models

A Coarse-Grained Biophysical Model of E. coli and Its Application to Perturbation of the rRNA Operon Copy Number

We propose a biophysical model of Escherichia coli that predicts growth rate and an effective cellular composition from an effective, coarse-grained representation of its genome. We assume that E. coli is in a state of balanced exponential steadystate growth, growing in a temporally and spatially constant environment, rich in resources. We apply this model to a series of past measurements, where the growth rate and rRNA-to-protein ratio have been measured for seven E. coli strains with an rRNA operon copy number ranging from one to seven (the wild-type copy number). These experiments show that growth rate markedly decreases for strains with fewer than six copies. Using the model, we were able to reproduce these measurements. We show that the model that best fits these data suggests that the volume fraction of macromolecules inside E. coli is not fixed when the rRNA operon copy number is varied. Moreover, the model predicts that increasing the copy number beyond seven results in a cytoplasm densely packed with ribosomes and proteins. Assuming that under such overcrowded conditions prolonged diffusion times tend to weaken binding affinities, the model predicts that growth rate will not increase substantially beyond the wild-type growth rate, as indicated by other experiments. Our model therefore suggests that changing the rRNA operon copy number of wild-type E. coli cells growing in a constant rich environment does not substantially increase their growth rate. Other observations regarding strains with an altered rRNA operon copy number, such as nucleoid compaction and the rRNA operon feedback response, appear to be qualitatively consistent with this model. In addition, we discuss possible design principles suggested by the model and propose further experiments to test its validity

Feasibility study into self-administered training at home using an arm and hand device with motivational gaming environment in chronic stroke

© 2015 Nijenhuis et al. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.BACKGROUND: Assistive and robotic training devices are increasingly used for rehabilitation of the hemiparetic arm after stroke, although applications for the wrist and hand are trailing behind. Furthermore, applying a training device in domestic settings may enable an increased training dose of functional arm and hand training. The objective of this study was to assess the feasibility and potential clinical changes associated with a technology-supported arm and hand training system at home for patients with chronic stroke. METHODS: A dynamic wrist and hand orthosis was combined with a remotely monitored user interface with motivational gaming environment for self-administered training at home. Twenty-four chronic stroke patients with impaired arm/hand function were recruited to use the training system at home for six weeks. Evaluation of feasibility involved training duration, usability and motivation. Clinical outcomes on arm/hand function, activity and participation were assessed before and after six weeks of training and at two-month follow-up. RESULTS: Mean System Usability Scale score was 69 % (SD 17 %), mean Intrinsic Motivation Inventory score was 5.2 (SD 0.9) points, and mean training duration per week was 105 (SD 66) minutes. Median Fugl-Meyer score improved from 37 (IQR 30) pre-training to 41 (IQR 32) post-training and was sustained at two-month follow-up (40 (IQR 32)). The Stroke Impact Scale improved from 56.3 (SD 13.2) pre-training to 60.0 (SD 13.9) post-training, with a trend at follow-up (59.8 (SD 15.2)). No significant improvements were found on the Action Research Arm Test and Motor Activity Log. CONCLUSIONS: Remotely monitored post-stroke training at home applying gaming exercises while physically supporting the wrist and hand showed to be feasible: participants were able and motivated to use the training system independently at home. Usability shows potential, although several usability issues need further attention. Upper extremity function and quality of life improved after training, although dexterity did not. These findings indicate that home-based arm and hand training with physical support from a dynamic orthosis is a feasible tool to enable self-administered practice at home. Such an approach enables practice without dependence on therapist availability, allowing an increase in training dose with respect to treatment in supervised settings. TRIAL REGISTRATION: This study has been registered at the Netherlands Trial Registry (NTR): NTR3669 .Peer reviewe

Colocalized Structural and Functional Changes in the Cortex of Patients with Trigeminal Neuropathic Pain

Background: Recent data suggests that in chronic pain there are changes in gray matter consistent with decreased brain volume, indicating that the disease process may produce morphological changes in the brains of those affected. However, no study has evaluated cortical thickness in relation to specific functional changes in evoked pain. In this study we sought to investigate structural (gray matter thickness) and functional (blood oxygenation dependent level – BOLD) changes in cortical regions of precisely matched patients with chronic trigeminal neuropathic pain (TNP) affecting the right maxillary (V2) division of the trigeminal nerve. The model has a number of advantages including the evaluation of specific changes that can be mapped to known somatotopic anatomy. Methodology/Principal Findings: Cortical regions were chosen based on sensory (Somatosensory cortex (SI and SII), motor (MI) and posterior insula), or emotional (DLPFC, Frontal, Anterior Insula, Cingulate) processing of pain. Both structural and functional (to brush-induced allodynia) scans were obtained and averaged from two different imaging sessions separated by 2–6 months in all patients. Age and gender-matched healthy controls were also scanned twice for cortical thickness measurement. Changes in cortical thickness of TNP patients were frequently colocalized and correlated with functional allodynic activations, and included both cortical thickening and thinning in sensorimotor regions, and predominantly thinning in emotional regions. Conclusions: Overall, such patterns of cortical thickness suggest a dynamic functionally-driven plasticity of the brain. These structural changes, which correlated with the pain duration, age-at-onset, pain intensity and cortical activity, may be specific targets for evaluating therapeutic interventions