Faithful Estimation of Dynamics Parameters from CPMG Relaxation Dispersion Measurements

This work examines the robustness of fitting of parameters describing conformational exchange (kex, pa/b, and Δω) processes from CPMG relaxation dispersion data. We have analyzed the equations describing conformational exchange processes for the intrinsic inter-dependence of their parameters that leads to the existence of multiple equivalent solutions, which equally satisfy the experimental data. We have used Monte-Carlo simulations and fitting to the synthetic data sets as well as the direct 3-D mapping of the parameter space of kex, pa/b, and Δω to quantitatively assess the degree of the parameter inter-dependence. The demonstrated high correlation between parameters can preclude accurate dynamics parameter estimation from NMR spin-relaxation data obtained at a single static magnetic field. The strong parameter inter-dependence can readily be overcome through acquisition of spin-relaxation data at more than one static magnetic field thereby allowing accurate assessment of conformational exchange properties

Soleus stretch reflex during cycling

The modulation and strength of the human soleus short latency stretch reflex was investigated by mechanically perturbing the ankle during an unconstrained pedaling task. Eight subjects pedaled at 60 rpm against a preload of 10 Nm. A torque pulse was applied to the crank at various positions during the crank cycle, producing ankle dorsiflexion perturbations of similar trajectory. The stretch reflex was greatest during the power phase of the crank cycle and was decreased to the level of background EMG during recovery. Matched perturbations were induced under static conditions at the same crank angle and background soleus EMG as recorded during the power phase of active pedaling. The magnitude of the stretch reflex was not statistically different from that during the static condition throughout the power phase of the movement. The results of this study indicate that the stretch reflex is not depressed during active cycling as has been shown with the H-reflex. This lack of depression may reflect a decreased susceptibility of the stretch reflex to inhibition, possibly originating from presynaptic mechanisms

Illusory Sensation of Movement Induced by Repetitive Transcranial Magnetic Stimulation

Human movement sense relies on both somatosensory feedback and on knowledge of the motor commands used to produce the movement. We have induced a movement illusion using repetitive transcranial magnetic stimulation over primary motor cortex and dorsal premotor cortex in the absence of limb movement and its associated somatosensory feedback. Afferent and efferent neural signalling was abolished in the arm with ischemic nerve block, and in the leg with spinal nerve block. Movement sensation was assessed following trains of high-frequency repetitive transcranial magnetic stimulation applied over primary motor cortex, dorsal premotor cortex, and a control area (posterior parietal cortex). Magnetic stimulation over primary motor cortex and dorsal premotor cortex produced a movement sensation that was significantly greater than stimulation over the control region. Movement sensation after dorsal premotor cortex stimulation was less affected by sensory and motor deprivation than was primary motor cortex stimulation. We propose that repetitive transcranial magnetic stimulation over dorsal premotor cortex produces a corollary discharge that is perceived as movement

Long-term motor skill training with individually adjusted progressive difficulty enhances learning and promotes corticospinal plasticity

Motor skill acquisition depends on central nervous plasticity. However, behavioural determinants leading to long lasting corticospinal plasticity and motor expertise remain unexplored. Here we investigate behavioural and electrophysiological effects of individually tailored progressive practice during long-term motor skill training. Two groups of participants practiced a visuomotor task requiring precise control of the right digiti minimi for 6 weeks. One group trained with constant task difficulty, while the other group trained with progressively increasing task difficulty, i.e. continuously adjusted to their individual skill level. Compared to constant practice, progressive practice resulted in a two-fold greater performance at an advanced task level and associated increases in corticospinal excitability. Differences were maintained 8 days later, whereas both groups demonstrated equal retention 14 months later. We demonstrate that progressive practice enhances motor skill learning and promotes corticospinal plasticity. These findings underline the importance of continuously challenging patients and athletes to promote neural plasticity, skilled performance, and recovery

The health informatics cohort enhancement project (HICE): using routinely collected primary care data to identify people with a lifetime diagnosis of psychotic disorder

Background: We have previously demonstrated that routinely collected primary care data can be used to identify potential participants for trials in depression [1]. Here we demonstrate how patients with psychotic disorders can be identified from primary care records for potential inclusion in a cohort study. We discuss the strengths and limitations of this approach; assess its potential value and report challenges encountered. Methods: We designed an algorithm with which we searched for patients with a lifetime diagnosis of psychotic disorders within the Secure Anonymised Information Linkage (SAIL) database of routinely collected health data. The algorithm was validated against the "gold standard" of a well established operational criteria checklist for psychotic and affective illness (OPCRIT). Case notes of 100 patients from a community mental health team (CMHT) in Swansea were studied of whom 80 had matched GP records. Results: The algorithm had favourable test characteristics, with a very good ability to detect patients with psychotic disorders (sensitivity > 0.7) and an excellent ability not to falsely identify patients with psychotic disorders (specificity > 0.9). Conclusions: With certain limitations our algorithm can be used to search the general practice data and reliably identify patients with psychotic disorders. This may be useful in identifying candidates for potential inclusion in cohort studies

Evaluation of a Brief Marriage Intervention for Internal Behavioral Health Consultants in Military Primary Care

Military couples face significant challenges to their relationships including demanding schedules, multiple deployments, and frequent moves. Despite the high costs of chronic marital distress, very few military (or civilian) couples seek marriage therapy. The military services and the VA system have implemented collaborative care models in primary care where internal behavioral health consultants are integrated into primary care. Integrated primary care can reduce the stigma of behavioral health services and may increase the odds that couples would seek help earlier. There are no established couple interventions designed for use in primary care. The purpose of this presentation is to describe a program of research focused on adapting and validating The Marriage Checkup (MC) for use in an integrated primary care clinic.https://corescholar.libraries.wright.edu/urop_celebration/1019/thumbnail.jp

IRE1β negatively regulates IRE1α signaling in response to endoplasmic reticulum stress

IRE1β is an ER stress sensor uniquely expressed in epithelial cells lining mucosal surfaces. Here, we show that intestinal epithelial cells expressing IRE1β have an attenuated unfolded protein response to ER stress. When modeled in HEK293 cells and with purified protein, IRE1β diminishes expression and inhibits signaling by the closely related stress sensor IRE1α. IRE1β can assemble with and inhibit IRE1α to suppress stress-induced XBP1 splicing, a key mediator of the unfolded protein response. In comparison to IRE1α, IRE1β has relatively weak XBP1 splicing activity, largely explained by a nonconserved amino acid in the kinase domain active site that impairs its phosphorylation and restricts oligomerization. This enables IRE1β to act as a dominant-negative suppressor of IRE1α and affect how barrier epithelial cells manage the response to stress at the host–environment interface