https://nova.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50653 Wed 28 Feb 2024 15:55:38 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:24304 485) (P < 0.01), p-PDPK-1 (Ser⁴¹) (P < 0.05), and PKCζ (P < 0.05) was higher in the PCUN and PIUN groups, and hepatic PDK4 (P < 0.001) and CPT-1 (P < 0.05) protein abundance was also higher in the PIUN twin fetus. We also found that the expression of a number of microRNAs was altered in response to PCUN or PIUN and that there is evidence that these changes may underlie the changes in the protein abundance of key regulators of hepatic fatty acid β-oxidation in the PCUN and PIUN groups. Therefore, embryo number and the timing of maternal undernutrition in early pregnancy have a differential impact on hepatic microRNA expression and on the factors that regulate hepatic fatty acid oxidation and lipid synthesis.]]> Wed 28 Feb 2024 15:22:08 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51924 Wed 28 Feb 2024 09:57:50 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:49742 Wed 26 Jun 2024 11:09:03 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:36884 Wed 26 Aug 2020 14:16:44 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:35659 Wed 24 Jun 2020 14:51:42 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51878 Wed 24 Jul 2024 15:56:39 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46431 Wed 23 Nov 2022 11:02:41 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:55346 Wed 22 May 2024 12:26:00 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:38603 Chlamydia trachomatis infection is a primary cause of reproductive tract diseases including infertility. Previous studies showed that this infection alters physiological activities in mouse oviducts. Whether this occurs in the uterus and cervix has never been investigated. This study characterized the physiological activities of the uterine horn and the cervix in a Chlamydia muridarum (Cmu)-infected mouse model at three infection time points of 7, 14, and 21 days postinfection (dpi). Cmu infection significantly decreased contractile force of spontaneous contraction in the cervix (7 and 14 dpi; P < 0.001 and P < 0.05, respectively), but this effect was not observed in the uterine horn. The responses of the uterine horn and cervix to oxytocin were significantly altered by Cmu infection at 7 dpi (P < 0.0001), but such responses were attenuated at 14 and 21 dpi. Cmu infection increased contractile force to prostaglandin (PGF2_α) by 53–83% in the uterine horn. This corresponded with the increased messenger ribonucleic acid (mRNA) expression of Ptgfr that encodes for its receptor. However, Cmu infection did not affect contractions of the uterine horn and cervix to PGE₂ and histamine. The mRNA expression of Otr and Ptger4 was inversely correlated with the mRNA expression of ll1b, ll6 in the uterine horn of Cmu-inoculated mice (P < 0.01 to P < 0.001), suggesting that the changes in the Otr and Ptger4mRNA expression might be linked to the changes in inflammatory cytokines. Lastly, this study also showed a novel physiological finding of the differential response to PGE₂ in mouse uterine horn and cervix.]]> Wed 17 Nov 2021 15:27:35 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:16571 Wed 11 Apr 2018 13:35:36 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:29840 T ≈ 0.25°C per pulse). Afferent spike trains evoked by heat pulse stimuli were diverse and included asynchronous inhibition, asynchronous excitation, and/or phase-locked APs synchronized to each infrared heat pulse. Thermal responses of membrane currents responsible for APs in ganglion neurons were strictly excitatory, with Q₁₀ ≈ 2. In contrast, hair cells responded with a mix of excitatory and inhibitory currents. Excitatory hair cell membrane currents included a thermoelectric capacitive current proportional to the rate of temperature rise (dT/dt) and an inward conduction current driven by ΔT. An iberiotoxin-sensitive inhibitory conduction current was also evoked by ΔT, rising in <3 ms and decaying with a time constant of ∼24 ms. The inhibitory component dominated whole cell currents in 50% of hair cells at −68 mV and in 67% of hair cells at −60 mV. Responses were quantified and described on the basis of first principles of thermodynamics. Results identify key molecular targets underlying heat pulse excitability in vestibular sensory organs and provide quantitative methods for rational application of optical heat pulses to examine protein biophysics and manipulate cellular excitability.]]> Wed 11 Apr 2018 09:55:53 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:23827 Wed 09 Feb 2022 15:57:43 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:52146 Wed 04 Oct 2023 10:20:41 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47290 Tue 30 Apr 2024 08:50:07 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46671 n = 4; 5,438 ± 783 pg/ml vs. control 193 ± 27 pg/ml, P < 0.05). Repeated hypoglycemia significantly reduced the plasma epinephrine response to subsequent hypoglycemia (n = 4; 2,179 ± 220 pg/ml vs. 5,438 ± 783 pg/ml, P < 0.05). Activation of medullary C1 (n = 4; 50 ± 5% vs. control 3 ± 1%, P < 0.05) and C3 (n = 4; 45 ± 5% vs. control 4 ± 1%, P < 0.05) neurons was significantly increased after a single episode of hypoglycemia. Activation of C1 (n = 4; 12 ± 3%, P < 0.05) and C3 (n = 4; 19 ± 5%, P < 0.05) neurons was significantly reduced in the HAAF groups. Hypoglycemia prevention or treatment with naloxone did not restore the plasma epinephrine response or C1 and C3 neuronal activation. Thus repeated hypoglycemia reduced the activation of C1 and C3 neurons mediating adrenal medullary responses to subsequent bouts of hypoglycemia.]]> Tue 29 Nov 2022 09:14:50 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47798 Tue 28 Mar 2023 15:16:40 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47641 Tue 24 Jan 2023 14:38:00 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:16911 Tue 24 Aug 2021 14:24:51 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:55700 Tue 18 Jun 2024 12:41:11 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45974 Tue 08 Nov 2022 14:19:06 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45897 Tue 08 Nov 2022 09:03:58 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:35651 84 cell monolayers grown on transparent, permeable supports was assessed over 48 h with or without bile acids. Cell migration was measured in Boyden chambers. mRNA and protein expression were measured by RT-PCR and Western blotting. DCA (50-150 μM) significantly inhibited wound closure in cultured epithelial monolayers and attenuated cell migration in Boyden chamber assays. DCA also induced nuclear accumulation of the farnesoid X receptor (FXR), whereas an FXR agonist, GW4064 (10 µM), inhibited wound closure. Both DCA and GW4064 attenuated the expression of CFTR Cl⁻ channels, whereas inhibition of CFTR activity with either CFTR-_inh-172 (10 μM) or GlyH-101 (25 µM) also prevented wound healing. Promoter/reporter assays revealed that FXR-induced downregulation of CFTR is mediated at the transcriptional level. In contrast, UDCA (50-150 µM) enhanced wound healing in vitro and prevented the effects of DCA. Finally, DCA inhibited and UDCA promoted mucosal healing in an in vivo mouse model. In conclusion, these studies suggest bile acids are important regulators of epithelial wound healing and are therefore good targets for development of new drugs to modulate intestinal barrier function in disease treatment. New & Noteworthy: The secondary bile acid, deoxycholic acid, inhibits colonic epithelial wound healing, an effect which appears to be mediated by activation of the nuclear bile acid receptor, FXR, with subsequent downregulation of CFTR expression and activity. In contrast, ursodeoxycholic acid promotes wound healing, suggesting it may provide an alternative approach to prevent the losses of barrier function that are associated with mucosal inflammation in IBD patients.]]> Tue 01 Oct 2019 13:39:00 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:55437 Thu 30 May 2024 14:32:42 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:35487 Thu 30 Jan 2020 13:53:08 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:37877 Thu 28 Oct 2021 13:02:25 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:38305 Thu 26 Aug 2021 11:11:37 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:36808 Thu 04 Nov 2021 10:39:56 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:34569 Thu 04 Nov 2021 10:38:24 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46830 Thu 01 Dec 2022 11:45:24 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:8433 Sat 24 Mar 2018 08:40:47 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:8251 Sat 24 Mar 2018 08:40:36 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:6928 41%). In older animals (P11–P25) this changed, with AP discharge consisting of brief bursts at current onset (~46% of neurons). Investigation of major subthreshold whole cell currents showed the rapid A-type potassium current (IAr) dominated at all ages examined (90% of neurons at E15–E17, decreasing to >50% after P10). IAr expression levels, based on peak current amplitude, increased during development. Steady-state inactivation and activation for IAr were slightly less potent in E15–E17 versus P21–P25 neurons at potentials near RMP (-55 mV). Together, our data indicate that intrinsic properties and IAr expression change dramatically in SDH neurons during development, with the greatest alterations occurring on either side of a critical period, P6–P10.]]> Sat 24 Mar 2018 08:40:23 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:7502 Sat 24 Mar 2018 08:38:33 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:993 Sat 24 Mar 2018 08:29:51 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:2825 Sat 24 Mar 2018 08:28:25 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:1436 Sat 24 Mar 2018 08:28:03 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:13869 Sat 24 Mar 2018 08:25:48 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:13287 Sat 24 Mar 2018 08:16:04 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:13289 2 = 0.31, P = 0.001), with RR variability (r² = 0.20, P = 0.008), and with systolic blood pressure (r² = 0.16, P = 0.02). Linear regression analysis identified the former two as independent predictors of QTVN. In conclusion, elevated repolarization lability is directly associated with sympathetic cardiac activation in patients with essential hypertension.]]> Sat 24 Mar 2018 08:16:04 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:11262 Sat 24 Mar 2018 08:10:52 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:12207 Sat 24 Mar 2018 08:08:25 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20824 Sat 24 Mar 2018 08:05:56 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:16909 A antagonist bicuculline methiodide (BMI; 40 pmol/100 nl) into the DMH-evoked increases in heart rate (HR), left ventricular pressure (LVP), myocardial contractility (LVdP/dt), arterial pressure, and respiratory rate. DMH disinhibition also precipitated multiple ventricular and supraventricular ectopic beats. DMH-induced increases in HR, LVP, LVdP/dt, and in the number of ectopic beats dependent on the side of stimulation, with R-DMH provoking larger responses. In contrast, pressor and respiratory responses did not depend on the side of stimulation. Newly described DMH-induced inotropic responses were rate-, preload- and (largely) afterload-independent; they were mediated by sympathetic cardiac pathway, as revealed by their sensitivity to β-adrenergic blockade. We conclude that recruitment of DMH neurons causes sympathetically mediated positive chronotropic and inotropic effects, and that there is an asymmetry, at the level of the DMH, in the potency to elicit these effects, with R-DMH > L-DMH.]]> Sat 24 Mar 2018 07:59:52 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:16908 Sat 24 Mar 2018 07:59:52 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:16912 A receptor antagonist) into sites within a circumscribed region in the deep layers of the superior colliculus and in the central and external nuclei of the inferior colliculus evoked a response characterized by intense and highly synchronized bursts of renal sympathetic nerve activity (RSNA) and phrenic nerve activity (PNA). Each burst of RSNA had a duration of ~300–400 ms and occurred slightly later (peak to peak latency of 41 ± 8 ms) than the corresponding burst of PNA. The bursts of RSNA and PNA were also accompanied by transient increases in arterial pressure and, in most cases, heart rate. Synchronized bursts of RSNA and PNA were also evoked after neuromuscular blockade, artificial ventilation, and vagotomy and so were not dependent on afferent feedback from the lungs. We propose that the synchronized sympathetic-respiratory responses are driven by a common population of neurons, which may normally be activated by an acute threatening stimulus.]]> Sat 24 Mar 2018 07:59:52 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:16910 Sat 24 Mar 2018 07:59:51 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20508 Sat 24 Mar 2018 07:59:05 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:5813 Sat 24 Mar 2018 07:48:02 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:5804 Sat 24 Mar 2018 07:44:54 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27703 Sat 24 Mar 2018 07:40:10 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:29786 Tnfsf10^−/−) mice were administered subcutaneous ovalbumin (OVA) followed by oral OVA challenges. In separate experiments, OVA-challenged mice were intraperitoneally administered salmeterol or dexamethasone. Esophageal biopsies from children with EoE revealed increased levels of TRAIL and MID-1 and reduced PP2A activation compared with controls. Tnfsf10^−/− mice were largely protected from esophageal fibrosis, eosinophilic inflammation, and the upregulation of TSLP, IL-5, IL-13, and CCL11 when compared with wild-type mice. Salmeterol administration to wild-type mice with experimental EoE restored PP2A activity and also prevented esophageal eosinophilia, inflammatory cytokine expression, and remodeling, which was comparable to the treatment effect of dexamethasone. TRAIL and PP2A regulate inflammation and fibrosis in experimental EoE, which can be therapeutically modulated by salmeterol.]]> Sat 24 Mar 2018 07:23:39 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:4459 Sat 24 Mar 2018 07:18:30 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:4460 Sat 24 Mar 2018 07:18:30 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:35649 A receptors (GABA_ARs) and glycine receptors (GlyRs). To assess their relative contribution to inhibition in the MVN, we recorded miniature inhibitory postsynaptic currents (mIPSCs) in physiologically characterized type A and type B MVN neurons. Transverse brain stem slices were prepared from mice (3–8 wk old), and whole cell patch-clamp recordings were obtained from visualized MVN neurons (CsCl internal; V_m = –70 mV; 23°C). In 81 MVN neurons, 69% received exclusively GABA_Aergic inputs, 6% exclusively glycinergic inputs, and 25% received both types of mIPSCs. The mean amplitude of GABA_AR-mediated mIPSCs was smaller than those mediated by GlyRs (22.6 ± 1.8 vs. 35.3 ± 5.3 pA). The rise time and decay time constants of GABAAR- versus GlyR-mediated mIPSCs were slower (1.3 ± 0.1 vs. 0.9 ± 0.1 ms and 10.5 ± 0.3 vs. 4.7 ± 0.3 ms, respectively). Comparison of type A (n = 20) and type B (n = 32) neurons showed that type A neurons received almost exclusively GABA_Aergic inhibitory inputs, whereas type B neurons received GABA_Aergic inputs, glycinergic inputs, or both. Intracellular labeling in a subset of MVN neurons showed that morphology was not related to a MVN neuron's inhibitory profile (n = 15), or whether it was classified as type A or B (n = 29). Together, these findings indicate that both GABA and glycine contribute to inhibitory synaptic processing in MVN neurons, although GABA dominates and there is a difference in the distribution of GABA_A and Gly receptors between type A and type B MVN neurons.]]> Mon 30 Sep 2019 14:53:51 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:11331 Mon 30 Sep 2019 12:33:52 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:16907 A miniature inhibitory postsynaptic current (mIPSC) amplitude was increased in spa and ot but not spd, suggesting diminished glycinergic drive leads to compensatory adjustments in the other major fast inhibitory synaptic transmitter system in these mutants. Overall, our data suggest long-term reduction in glycinergic drive to HMs results in changes in intrinsic and synaptic properties that are consistent with homeostatic plasticity in spa and ot but not in spd. We propose such plasticity is an attempt to stabilize HM output, which succeeds in spa but fails in ot.]]> Mon 30 Sep 2019 12:26:58 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22855 Mon 30 Sep 2019 12:19:51 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27677 Mon 30 Sep 2019 11:23:54 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:52855 92%). Short-term plasticity was studied by examining discharge rate modulation following release from hyperpolarization [postinhibitory rebound firing (PRF)] and depolarization [firing rate adaptation (FRA)]. PRF and FRA gain were similar in Deiters’ and non-Deiters’ neurons (PRF 24.9 vs. 20.2 Hz and FRA gain 231.5 vs. 287.8 spikes/s/nA, respectively). Inhibitory synaptic input to both populations showed that GABAergic rather than glycinergic inhibition dominated. However, GABAA miniature inhibitory postsynaptic current (mIPSC) frequency was much higher in Deiters’ neurons compared with non-Deiters’ neurons (∼15.9 vs. 1.4 Hz, respectively). Our data suggest that Deiters’ neurons can be reliably identified by their intrinsic membrane and synaptic properties. They are tonically active and glutamatergic, have low sensitivity or “gain,” exhibit little adaptation, and receive strong GABAergic input. Deiters’ neurons also have minimal short-term plasticity, and together these features suggest they are well suited to a role in encoding tonic signals for the vestibulospinal reflex. New & Noteworthy: Deiters’ neurons within the lateral vestibular nucleus project the length of the spinal cord and activate antigravity extensor muscles. Deiters’ neurons were characterized anatomically and physiologically in mice. Deiters’ neurons are tonically active, have homogeneous intrinsic membrane properties, including low input resistance, and receive significant GABAAergic synaptic inputs. Deiters’ neurons show little modulation in response to current injection. These features are consistent with Deiters’ neurons responding to perturbations to maintain posture and balance.]]> Mon 30 Oct 2023 09:54:00 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:38353 Mon 30 Aug 2021 16:06:38 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47532 0.05) different from that of cardiac and respiratory modulation at rest (47.1%, 18.7–56.3% and 48.6%, 28.4–59.3%, respectively) or during sinusoidal displacement (10.3%, 6.2–32.1% and 26.9%, 13.6–43.3%, respectively). Respiratory frequency was entrained above its resting rate (0.26 Hz, 0.2–0.29 Hz) during sinusoidal neck displacement; there was no significant difference (P > 0.05) between respiratory frequency (0.38 Hz, 0.25–0.49 Hz) and sinusoidal displacement frequency (0.39 Hz, 0.35–0.42 Hz). This study provides evidence that SSNA is modulated during neck movement, raising the possibility that neck mechanoreceptors may contribute to the cutaneous vasoconstriction and sweat release associated with motion sickness. New & Noteworthy: This study demonstrates that dynamic, but not static, stretching of the neck modulates skin sympathetic nerve activity in the lower limbs.]]> Mon 23 Jan 2023 12:22:52 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:42376 Mon 22 Aug 2022 14:29:29 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:35652 Mon 20 Nov 2023 11:12:20 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:35650 Mon 13 Nov 2023 11:04:35 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:36049 Fri 31 Jan 2020 13:13:08 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:12206 10%. Distortion of pulsed Doppler signal peaks occurred in the conscious rabbit at peak aortic velocities, at which Reynold's number for turbulence was exceeded and the Doppler shift surpassed the Nyquist limit of 31.25 kHz for the velocimeter. Although the Doppler shift-volume flow relationship is linear at < 5 kHz, in some cases at higher Doppler shifts and blood flow velocities the relationship may become nonlinear, thus causing the volume flow rate to be underestimated by up to 38%. The cause of this phenomenon may be "aliasing" and/or the consequence of the range control capability of the velocimeter selectively sampling changing velocity profiles and flow disturbances in the central stream at higher velocities.]]> Fri 27 Sep 2019 16:32:00 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:12405 br), Q_br conductance (C_br), bronchial hemicircumference (CIRC_br), and bronchial wall thickness (WALL TH_br) in recovered, standing, awake sheep. Methacholine (MCh; 0.125–2.0 μg/kg iv), at the highest dose, caused a 233% rise in Qbr (P < 0.05) and a 286% rise in C_br (P < 0.05). CIRC_br fell to 90% (P < 0.05); WALL TH_br did not change. In contrast, nebulized MCh (1–32 mg/ml), inhaled through a mask at the highest dose, caused a rise in ventilation and a rise in Qbr proportional to aortic pressure without change in C_br. CIRC_br fell to 91% (P < 0.01), and WALL TH_br did not change. Thus inhaled MCh has access to cholinoceptors of bronchial circumferential smooth muscle to cause airway lumen narrowing but effectively not to those of the systemic bronchovascular circulation. It is speculated that the mechanism is selective neuroparacrine inhibition of muscarinic acetylcholine receptors (M3 bronchovascular cholinoceptors) by prostanoids released by intense MCh activation of epithelial and mucosal cells lining the airway.]]> Fri 27 Sep 2019 16:25:54 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:12664 τ) has been calculated in dogs from the rearranged Kubicek formula: p_τ = (SV · Z₀²)/(L² dZ/dt_max·T), where SV was measured by the electromagnetic flowmeter (EM). Hematocrit (Hct) in the dog was varied by hemorrhage and infusion. In contrast to the direct and exponential bench p-Hct relationship, p_τ varies inversely with Hct, but by no more than +6.3 Ω · cm (at Hct 26%) and -11.8 Ω · cm (at Hct 66%) about a mean p_τ of 135 ± 1.0 Ω · cm (at Hct 40%). Impedance SV calculated using p_τ over a wide range of SV bears a linear relationship to EM values with a 95% prediction limit for a single SV estimate of ±0.84 about a mean value of 26.9 ml. The findings suggest that p_τ is virtually constant during a variety of physiological disturbances.]]> Fri 27 Sep 2019 16:12:28 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:12670 Fri 27 Sep 2019 16:03:24 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:12671 Fri 27 Sep 2019 15:57:40 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:12704 Fri 27 Sep 2019 15:45:17 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:34081 Fri 27 Sep 2019 10:22:06 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:42207 2) during planned bariatric surgery. Compared with subcutaneous adipose tissue, visceral adipose tissue exhibited decreased complex II activity, which was restored with the reducing agent dithiothreitol (5 mM) (P < 0.01). A biotin switch assay identified that cysteine oxidative posttranslational modifications (OPTM) in complex II subunit A (succinate dehydrogenase A) were increased in visceral vs. subcutaneous fat (P < 0.05). Insulin treatment (100 nM) stimulated complex II activity in subcutaneous fat (P < 0.05). In contrast, insulin treatment of visceral fat led to a decrease in complex II activity (P < 0.01), which was restored with addition of the mitochondria-specific oxidant scavenger mito-TEMPO (10 µM). In a cohort of 10 subjects with severe obesity, surgical weight loss decreased OPTM and restored complex II activity, exclusively in the visceral depot. Mitochondrial complex II may be an unrecognized and novel mediator of insulin resistance associated with visceral adiposity. The activity of complex II is improved by weight loss, which may contribute to metabolic improvements associated with bariatric surgery.]]> Fri 26 Aug 2022 09:16:37 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:35648 -/-) mice. Immunostaining for choline acetyltransferase revealed there were no obvious gross morphological differences in the peripheral EVS innervation among any of these strains. ACh application onto wt type II hair cells, at resting potentials, produced a fast inward current followed by a slower outward current, resulting in membrane hyperpolarization and decreased membrane resistance. Hyperpolarization and decreased resistance were due to gating of SK channels. Consistent with activation of a9*nAChRs and SK channels, these ACh-sensitive currents were antagonized by the a9*nAChR blocker strychnine and SK blockers apamin and tamapin. Type II hair cells from a9^-/- mice, however, failed to respond to ACh at all. These results confirm the critical importance of a9nAChRs in efferent modulation of mammalian type II vestibular hair cells. Application of exogenous ACh reduces electrical impedance, thereby decreasing type II hair cell sensitivity. NEW & NOTEWORTHY Expression of a9 nicotinic subunit was crucial for fast cholinergic modulation of mammalian vestibular type II hair cells. These findings show a multifaceted efferent mechanism for altering hair cell membrane potential and decreasing membrane resistance that should reduce sensitivity to hair bundle displacements.]]> Fri 18 Aug 2023 10:20:28 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48450 Fri 17 Mar 2023 09:25:55 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:25370 Fri 16 Aug 2024 17:15:25 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51239 Fri 10 Nov 2023 07:15:55 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:49107 Fri 05 May 2023 11:32:08 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:41554 Fri 05 Aug 2022 14:23:21 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:36769 Fri 03 Jul 2020 14:34:42 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:24090 Aspergillus fumigatus allergen mouse model of EoE. Because IL-33 induction was transient in this model and chronicity of IL-33 expression has been demonstrated in humans, naive mice were treated with recombinant IL-33 for 1 wk and esophageal pathology was evaluated. IL-33 application produced changes consistent with phenotypically early EoE, including transmural eosinophilia, mucosal hyperproliferation, and upregulation of eosinophilic genes and chemokines. Th2 cytokines, including IL-13, along with innate lymphoid cell group 2, Th1/17, and M2 macrophage marker genes, were increased after IL-33 application. IL-33-induced eosinophilia was ablated in IL-13 null mice. In addition, IL-33 induced a profound inhibition of the regulatory T cell gene signature. We conclude that IL-33 gene expression is associated with pediatric EoE development and that application of recombinant protein in mice phenocopies the early clinical phase of the human disease in an IL-13-dependent manner. IL-33 inhibition of esophageal regulatory T cell function may induce loss of antigenic tolerance, thereby providing a mechanistic rationale for EoE development.]]> Fri 03 Dec 2021 10:32:37 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33480 -/-) BALB/c mice were infected intranasally with RV1B. In separate experiments, Tnfsf10^-/- mice were sensitized and challenged via the airway route with house dust mite (HDM) to induce allergic airways disease and then challenged with RVIB or UV-RVIB. Airway hyperreactivity (AHR) was invasively assessed as total airways resistance in response to increasing methacholine challenge and inflammation was assessed in bronchoalveolar lavage fluid at multiple time points postinfection. Chemokines were quantified by ELISA of whole lung lysates and viral load was determined by quantitative RT-PCR and tissue culture infective dose (TCID₅₀). Human airway epithelial cells (BEAS2B) were infected with RV1B and stimulated with recombinant TRAIL or neutralizing anti-TRAIL antibodies and viral titer assessed by TCID₅₀. HDM-challenged Tnfsf10 ^-/- mice were protected against RV-induced AHR and had suppressed cellular infiltration in the airways upon RV infection. Chemokine C-X-C-motif ligand 2 (CXCL2) production was suppressed in naïve Tnfsf10^-/- mice infected with RV1B, with less RV1B detected 24 h postinfection. This was associated with reduced apoptotic cell death and a reduction of interferon (IFN)-λ2/3 but not IFN-α or IFN-β. TRAIL stimulation increased, whereas anti-TRAIL antibodies reduced viral replication in RV1B-infected BEAS2B cells in vitro. In conclusion, TRAIL promotes RV-induced AHR, inflammation and RV1B replication, implicating this molecule and its downstream signaling pathways as a possible target for the amelioration of RV1B-induced allergic and nonallergic lung inflammation and AHR.]]> Fri 01 Apr 2022 09:25:03 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33085 -/-) and TLR4-deficient (Tlr4^-/-) mice. CS-induced airway fibrosis, characterized by increased collagen deposition around small airways, was not altered in Tlr2^-/- mice but was attenuated in Tlr4^-/- mice compared with CS-exposed WT controls. However, Tlr2^-/- mice had increased CS-induced emphysema-like alveolar enlargement, apoptosis, and impaired lung function, while these features were reduced in Tlr4^-/- mice compared with CS-exposed WT controls. Taken together, these data highlight the complex roles of TLRs in the pathogenesis of COPD and suggest that activation of TLR2 and/or inhibition of TLR4 may be novel therapeutic strategies for the treatment of COPD.]]> Fri 01 Apr 2022 09:24:33 AEDT ]]>