CD28 Ligation Increases Macrophage Suppression of T Cell Proliferation

When compared to spleen or lymph node cells, resident peritoneal cavity cells respond poorly to T cell activation in vitro. The greater proportional representation of macrophages in this cell source has been shown to actively suppress the T cell response. Peritoneal macrophages exhibit an immature phenotype $(MHC Class II^{lo}, B7^{lo})$ that reduces their efficacy as antigen presenting cells. Furthermore, these cells readily express inducible nitric oxide synthase (iNOS), an enzyme that promotes T cell tolerance by catabolism of the limiting amino acid arginine. Here, we investigate the ability of exogenous T cell costimulation to recover the peritoneal T cell response. We show that CD28 ligation failed to recover the peritoneal T cell response and actually suppressed responses that had been recovered by inhibiting iNOS. As indicated by cytokine ELISpot and neutralizing mAb treatment, this “co-suppression” response was due to CD28 ligation increasing the number of IFNγ-secreting cells. Our results illustrate that cellular composition and cytokine milieu influence T cell costimulation biology

Central Serotonergic Neurons Activate and Recruit Thermogenic Brown and Beige Fat and Regulate Glucose and Lipid Homeostasis

SummaryThermogenic brown and beige adipocytes convert chemical energy to heat by metabolizing glucose and lipids. Serotonin (5-HT) neurons in the CNS are essential for thermoregulation and accordingly may control metabolic activity of thermogenic fat. To test this, we generated mice in which the human diphtheria toxin receptor (DTR) was selectively expressed in central 5-HT neurons. Treatment with diphtheria toxin (DT) eliminated 5-HT neurons and caused loss of thermoregulation, brown adipose tissue (BAT) steatosis, and a >50% decrease in uncoupling protein 1 (Ucp1) expression in BAT and inguinal white adipose tissue (WAT). In parallel, blood glucose increased 3.5-fold, free fatty acids 13.4-fold, and triglycerides 6.5-fold. Similar BAT and beige fat defects occurred in Lmx1bf/fePet1Cre mice in which 5-HT neurons fail to develop in utero. We conclude 5-HT neurons play a major role in regulating glucose and lipid homeostasis, in part through recruitment and metabolic activation of brown and beige adipocytes

2015 Research & Innovation Day Program

A one day showcase of applied research, social innovation, scholarship projects and activities.https://first.fanshawec.ca/cri_cripublications/1002/thumbnail.jp

Can Electrocochleography Help Preserve Hearing After Cochlear Implantation With Full Electrode Insertion?

Objectives To evaluate the utility of intracochlear electrocochleography (ECochG) monitoring during cochlear implant (CI) surgery on postoperative hearing preservation. Study Design Prospective, randomized clinical trial. Setting Ten high-volume, tertiary care CI centers. Patients Adult patients with sensorineural hearing loss meeting the CI criteria who selected an Advanced Bionics CI. Methods Patients were randomized to CI surgery either with audible ECochG monitoring available to the surgeon during electrode insertion or without ECochG monitoring. Hearing preservation was determined by comparing preoperative unaided low-frequency (125-, 250-, and 500-Hz) pure-tone average (LF-PTA) to postoperative LF-PTA at CI activation. Pre- and post-CI computed tomography was used to determine electrode scalar location and electrode translocation. Results Eighty-five adult CI candidates were enrolled. The mean (standard deviation [SD]) unaided preoperative LF-PTA across the sample was 54 (17) dB HL. For the whole sample, hearing preservation was "good" (i.e., LF-PTA change 0-15 dB) in 34.5%, "fair" (i.e., LF-PTA change >15-29 dB) in 22.5%, and "poor" (i.e., LF-PTA change >= 30 dB) in 43%. For patients randomized to ECochG "on," mean (SD) LF-PTA change was 27 (20) dB compared with 27 (23) dB for patients randomized to ECochG "off" (p = 0.89). Seven percent of patients, all of whom were randomized to ECochG off, showed electrode translocation from the scala tympani into the scala vestibuli. Conclusions Although intracochlear ECochG during CI surgery has important prognostic utility, our data did not show significantly better hearing preservation in patients randomized to ECochG "on" compared with ECochG "off.

Overground walking with a robotic exoskeleton elicits trunk muscle activity in people with high-thoracic motor-complete spinal cord injury

Background: The trunk muscles are critical for postural control. Recent neurophysiological studies have revealed sparing of trunk muscle function in individuals with spinal cord injury (SCI) classified with thoracic or cervical motor-complete injuries. These findings raise the possibility for recruiting and retraining this spared trunk function through rehabilitation. Robotic gait training devices may provide a means to promote trunk muscle activation. Thus, the objective of this study was to characterize and compare the activation of the trunk muscles during walking with two robotic gait training devices (Ekso and Lokomat) in people with high thoracic motor-complete SCI. Methods: Participants with chronic motor-complete paraplegia performed 3 speed-matched walking conditions: Lokomat-assisted walking, Ekso-assisted walking overground, and Ekso-assisted walking on a treadmill. Surface electromyography (EMG) signals were recorded bilaterally from the rectus abdominis (RA), external oblique (EO), and erector spinae (ES) muscles. Results: Greater recruitment of trunk muscle EMG was elicited with Ekso-assisted walking compared to the Lokomat. Similar levels of trunk EMG activation were observed between Ekso overground and Ekso on the treadmill, indicating that differences between Ekso and Lokomat could not be attributed to the use of a hand-held gait aid. The level of trunk EMG activation during Lokomat walking was not different than that recorded during quiescent supine lying. Conclusions: Ekso-assisted walking elicits greater activation of trunk muscles compared to Lokomat-assisted walking, even after controlling for the use of hand-held assistive devices. The requirement of the Ekso for lateral weight-shifting in order to activate each step could lead to better postural muscle activation.Education, Faculty ofOther UBCKinesiology, School ofReviewedFacult