Frontiers in physiology
-
Frontiers in physiology · Jan 2017
Maximal Voluntary Activation of the Elbow Flexors Is under Predicted by Transcranial Magnetic Stimulation Compared to Motor Point Stimulation Prior to and Following Muscle Fatigue.
Transcranial magnetic (TMS) and motor point stimulation have been used to determine voluntary activation (VA). However, very few studies have directly compared the two stimulation techniques for assessing VA of the elbow flexors. The purpose of this study was to compare TMS and motor point stimulation for assessing VA in non-fatigued and fatigued elbow flexors. ⋯ There was no change in triceps/biceps electromyography, biceps/triceps MEP amplitudes, or bicep MEP amplitudes throughout the fatigue protocol at 100% MVC. In conclusion, motor point stimulation as opposed to TMS led to a higher estimation of VA in non-fatigued and fatigued elbow flexors. The decreased linear relationship between TMS superimposed twitch force and voluntary force led to an underestimation of the estimated resting twitch force and thus, a reduced VA.
-
Frontiers in physiology · Jan 2017
Human COQ9 Rescues a coq9 Yeast Mutant by Enhancing Coenzyme Q Biosynthesis from 4-Hydroxybenzoic Acid and Stabilizing the CoQ-Synthome.
Coq9 is required for the stability of a mitochondrial multi-subunit complex, termed the CoQ-synthome, and the deamination step of Q intermediates that derive from para-aminobenzoic acid (pABA) in yeast. In human, mutations in the COQ9 gene cause neonatal-onset primary Q10 deficiency. In this study, we determined whether expression of human COQ9 could complement yeast coq9 point or null mutants. ⋯ A small amount of the human COQ9 co-purified with tagged Coq6, Coq6-CNAP, indicating that human COQ9 interacts with the yeast Q-biosynthetic complex. These findings suggest that human COQ9 rescues the yeast coq9 temperature-sensitive mutant by stabilizing the CoQ-synthome and increasing Q biosynthesis from 4HB. This finding provides a powerful approach to studying the function of human COQ9 using yeast as a model.
-
Frontiers in physiology · Jan 2017
Distinct Mechanism of Cysteine Oxidation-Dependent Activation and Cold Sensitization of Human Transient Receptor Potential Ankyrin 1 Channel by High and Low Oxaliplatin.
Oxaliplatin, a third-generation platinum-based chemotherapeutic agent, displays unique acute peripheral neuropathy triggered or enhanced by cold, and accumulating evidence suggests that transient receptor potential ankyrin 1 (TRPA1) is responsible. TRPA1 is activated by oxaliplatin via a glutathione-sensitive mechanism. However, oxaliplatin interrupts hydroxylation of a proline residue located in the N-terminal region of TRPA1 via inhibition of prolyl hydroxylase (PHD), which causes sensitization of TRPA1 to reactive oxygen species (ROS). ⋯ By contrast, a lower concentration of oxaliplatin (100 μM) did not increase the intracellular Ca2+ concentration but did confer cold sensitivity on hTRPA1-expressing cells, and this was inhibited by PHD2 co-overexpression. Cold sensitivity was abolished by the mitochondria-targeting ROS scavenger mitoTEMPO and was minimal in cysteine-mutated hTRPA1 (Cys641Ser or Cys665Ser)-expressing cells. Thus, high oxaliplatin evokes ROS-mediated cysteine oxidation-dependent hTRPA1 activation independent of PHD activity, while a lower concentration induces cold-induced cysteine oxidation-dependent opening of hTRPA1 via PHD inhibition.
-
Frontiers in physiology · Jan 2017
The Regulatory Effects of Lateral Hypothalamus Area GABAB Receptor on Gastric Ischemia-Reperfusion Injury in Rats.
HIGHLIGHTS The aim of the research was to determine the functional effects and molecular mechanisms of GABAB receptor on ischemia reperfusion-induced gastric injury in rats. The lateral hypothalamus area GABAB receptor attenuated the ischemia reperfusion-induced gastric injury by up-regulating the production of GABA, GABABR, and down-regulating P-GABABR in the brain. This work would provide a new therapeutic strategy for acute gastric injury. ⋯ Pretreatment with GABAB receptor antagonist CGP35348 reversed the protective effects of FN stimulation or baclofen into the LHA. Microinjection of baclofen into the LHA obviously reduced the expression of inflammatory factor IL-1β, NOX2, and NOX4 in the gastric mucosa. Conclusion: The protective effects of microinjection of GABABR agonist into LHA on GI-R injury in rats could be mediated by up-regulating the production of GABA, GABABR, and down-regulating P-GABABR in the LHA.
-
Frontiers in physiology · Jan 2017
Multiparametric Renal Magnetic Resonance Imaging: Validation, Interventions, and Alterations in Chronic Kidney Disease.
Background: This paper outlines a multiparametric renal MRI acquisition and analysis protocol to allow non-invasive assessment of hemodynamics (renal artery blood flow and perfusion), oxygenation (BOLD T2*), and microstructure (diffusion, T1 mapping). Methods: We use our multiparametric renal MRI protocol to provide (1) a comprehensive set of MRI parameters [renal artery and vein blood flow, perfusion, T1, T2*, diffusion (ADC, D, D*, fp), and total kidney volume] in a large cohort of healthy participants (127 participants with mean age of 41 ± 19 years) and show the MR field strength (1.5 T vs. 3 T) dependence of T1 and T2* relaxation times; (2) the repeatability of multiparametric MRI measures in 11 healthy participants; (3) changes in MRI measures in response to hypercapnic and hyperoxic modulations in six healthy participants; and (4) pilot data showing the application of the multiparametric protocol in 11 patients with Chronic Kidney Disease (CKD). Results: Baseline measures were in-line with literature values, and as expected, T1-values were longer at 3 T compared with 1.5 T, with increased T1 corticomedullary differentiation at 3 T. ⋯ No significant difference was found in renal T2*. Conclusions: Multiparametric MRI is a powerful technique for the assessment of changes in structure, hemodynamics, and oxygenation in a single scan session. This protocol provides the potential to assess the pathophysiological mechanisms in various etiologies of renal disease, and to assess the efficacy of drug treatments.