266 research outputs found

    Intense isolectin-B4 binding in rat dorsal root ganglion neurons distinguishes c-fiber nociceptors with broad action potentials and high nav1.9 expression

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    Binding to isolectin-B4 (IB4) and expression of tyrosine kinase A (trkA) (the high-affinity NGF receptor) have been used to define two different subgroups of nociceptive small dorsal root ganglion (DRG) neurons. We previously showed that only nociceptors have high trkA levels. However, information about sensory and electrophysiological properties in vivo of single identified IB4-binding neurons, and about their trkA expression levels, is lacking. IB4-positive (IB4+) and small dark neurons had similar size distributions. We examined IB4-binding levels in >120 dye-injected DRG neurons with sensory and electrophysiological properties recorded in vivo. Relative immunointensities for trkA and two TTX-resistant sodium channels (Nav1.8 and Nav1.9) were also measured in these neurons. IB4+ neurons were classified as strongly or weakly IB4+. All strongly IB4+ neurons were C-nociceptor type (C-fiber nociceptive or unresponsive). Of 32 C-nociceptor-type neurons examined, ~50% were strongly IB4+, ~20% were weakly IB4+ and ~30% were IB4–. A{delta} low-threshold mechanoreceptive (LTM) neurons were weakly IB4+ or IB4–. All 33 A-fiber nociceptors and all 44 A{alpha}/beta-LTM neurons examined were IB4–. IB4+ compared with IB4– C-nociceptor-type neurons had longer somatic action potential durations and rise times, slower conduction velocities, more negative membrane potentials, and greater immunointensities for Nav1.9 but not Nav1.8. Immunointensities of IB4 binding in C-neurons were positively correlated with those of Nav1.9 but not Nav1.8. Of 23 C-neurons tested for both trkA and IB4, ~35% were trkA+/IB4+ but with negatively correlated immunointensities; 26% were IB4+/trkA–, and 35% were IB4–/trkA+. We conclude that strongly IB4+ DRG neurons are exclusively C-nociceptor type and that high Nav1.9 expression may contribute to their distinct membrane properties

    An investigation of Physics undergraduates’ attitudes towards mathematics

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    In recent years, the failure rate on first year mathematics modules on Physics courses at Loughborough University has given cause for concern. It was feared that failure in the first year would result in students performing poorly in future mathematics modules. Hence, a proactive support system was introduced for the mathematically less well-prepared first year Physics students in October 2005. On completion of the first mathematics module, this initiative showed some successful features in terms of the results of the less well-prepared students. However, the use of qualitative research methods revealed a difference in attitudes towards mathematics between the wellprepared and less well-prepared students. This paper outlines the students’ attitudes towards mathematics expressed through questionnaires and individual interviews. It compares the well-prepared and less well-prepared students’ attitudes towards mathematics prior to university and discusses the differences between the two cohorts. The paper also examines how the introduction of a support system has affected the students’ attitudes. A key outcome, in terms of the less well-prepared students, is that the first semester experience was positive in terms of increasing enjoyment of mathematics, but was negative in terms of feeling confident in mathematics. Finally, the paper also analyses data taken from individual interviews with some students on students’ learning approaches towards mathematics. These are investigated closely and comparisons are again made between the well-prepared and less well-prepared students. The analysis reveals that the less well-prepared students failed to adapt their learning approach to one suitable for Higher Education

    Maternal undernutrition and the ovine acute phase response to vaccination

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    Background: The acute phase response is the immediate host response to infection, inflammation and trauma and can be monitored by measuring the acute phase proteins (APP) such as haptoglobin ( Hp) or serum amyloid A (SAA). The plane of nutrition during pregnancy is known to affect many mechanisms including the neuroendocrine and neuroimmune systems in neonatal animals but effects on the APP are unknown. To investigate this phenomenon the serum concentration of Hp and SAA was initially determined in non-stimulated lambs from 3 groups (n = 10/group). The dams of the lambs of the respective groups were fed 100% of requirements throughout gestation (High/High; HH); 100% of requirements for the first 65 d of gestation followed by 70% of requirements until 125 d from when they were fed 100% of requirements (High/Low; HL); 65% of liveweight maintenance requirements for the first 65 d gestation followed by 100% of requirements for the remainder of pregnancy ( Low/High; LH). The dynamic APP response in the lambs was estimated by measuring the concentration of Hp and SAA following routine vaccination with a multivalent clostridial vaccine with a Pasteurella component, Heptavac P (TM) following primary and secondary vaccination. Results: The Hp and SAA concentrations were significantly lower at the time of vaccination ( day 8-14) than on the day of birth. Vaccination stimulated the acute phase response in lambs with increases found in both Hp and SAA. Maternal undernutrition led to the SAA response to vaccination being significantly lower in the HL group than in the HH group. The LH group did not differ significantly from either the HH or HL groups. No significant effects of maternal undernutrition were found on the Hp concentrations. A significant reduction was found in all groups in the response of SAA following the second vaccination compared to the response after the primary vaccination but no change occurred in the Hp response. Conclusion: Decreased SAA concentrations, post-vaccination, in lambs born to ewes on the HL diet shows that maternal undernutrition prior to parturition affects the innate immune system of the offspring. The differences in response of Hp and SAA to primary and secondary vaccinations indicate that the cytokine driven APP response mechanisms vary with individual AP

    Caspase-9 inhibition confers stronger neuronal and vascular protection compared to VEGF neutralization in a mouse model of retinal vein occlusion

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    PurposeRetinal vein occlusion (RVO) is a sight-threatening condition typically treated with intravitreal injection of vascular endothelial growth factor (VEGF) antagonists. Treatment response to anti-VEGF therapies is highly variable, with poor visual outcomes and treatment response in patients with significant retinal nonperfusion following RVO. Recently, caspase-9 has been identified as a potent regulator of edema, gliosis, and neuronal dysfunction during acute retinal hypoxia. The purpose of this study was to compare the therapeutic effect of caspase-9 inhibition against VEGF-neutralization in an established mouse model of RVO.MethodsAdult male C57Bl/6 J mice were randomized to induction of RVO and treatment with either vehicle, intravitreal injection of anti-VEGF antibody, topical administration of a selective caspase-9 inhibitor (Pen1-XBir3), or a combination therapy. Animals were followed on days 1, 2, and 8 after RVO with fundus retinal imaging, and with optical coherence tomography (OCT) to capture retinal swelling, capillary nonperfusion (measured by disorganization of retinal inner layers, DRIL), hyperreflective foci (HRF), and retinal atrophy. Focal electroretinography (ERG) measurements were performed on day 7. Histology was performed on retinal sections from day 8.ResultsBoth VEGF neutralization and caspase-9 inhibition showed significant retinal protection from RVO compared to vehicle treatment arm. Retinal reperfusion of occluded veins was accelerated in eyes receiving caspase-9 inhibitor, but not significantly different from vehicle in the anti-VEGF group. Retinal edema was suppressed in all treatment groups, with approximately 2-fold greater edema reduction with caspase-9 inhibition compared to VEGF neutralization. HRF were reduced similarly across all treatment groups compared to vehicle. Retinal detachment was reduced only in eyes treated with caspase-9 inhibitor monotherapy. Caspase-9 inhibition reduced retinal atrophy and preserved ERG response; VEGF neutralization did not prevent neurodegeneration following RVO.ConclusionCaspase-9 inhibition confers stronger neuronal and vascular protection compared to VEGF neutralization in the mouse laser-induced model of RVO

    Reading for Charles Burchfield

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    Featuring poets who participated in the March 8th Heat Waves in a Swamp workshop

    Growth kinetic parameters and prediction of growth and zearalenone and deoxynivalenol production boundaries by three Fusarium asiaticum strains isolated from wheat

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    Fusarium species can cause head blight of cereals worldwide. This is accompanied by impacts on yield and contamination of grains with mycotoxins. Regulations, with maximum limits, exist for the relevant Fusarium mycotoxins (e.g., type A and B trichothecenes, zearalenone and fumonisins). There is interest in a better understanding of the effect of key interacting abiotic factors which determine colonization and mycotoxin production in small grain cereals. Thus, this study examined the ecophysiological relationship between temperature and water availability (10–35 °C; water activity, aw, 0.87–0.98) on growth and production of Fusarium mycotoxins (zearelenone, ZEA; deoxynivalenol, DON; 3-acetyl deoxynivalenol, 3-Ac-DON and nivalenol, NIV) by three strains of F. asiaticum, a head blight pathogen isolated from China and becoming important in other global regions. These were carried out on simulated wheat-based matrices that identified the optimum (25 °C/0.98 aw) and marginal boundary conditions for growth (35 °C/0.90 aw) for all three strains. Contrarily, different mycotoxigenic profiles were observed between strains (p < 0.05). Four mycotoxins assessed were produced at 30 °C while cold temperature inhibited the production of NIV and ZEA, which were never detected at <20 and <15 °C, respectively. Optimal mycotoxin production conditions varied for each toxin with ZEA production which was best at 30 °C/0.93–0.95 aw, DON, 3-Ac-DON and NIV which was 0.98 aw/20–30 °C. Probabilistic models were used to predict growth and regulated mycotoxin production by the strains of F. asiaticum. This study will be beneficial in the development mitigation strategies for control of pre- and post-harvest colonization of cereals and mycotoxin contamination by this Fusarium species in cereals
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