Extracellular signal-regulated kinases mediate the enhancing effects of inflammatory mediators on resurgent currents in dorsal root ganglion neurons

Previously we reported that a group of inflammatory mediators significantly enhanced resurgent currents in dorsal root ganglion neurons. To understand the underlying intracellular signaling mechanism, we investigated the effects of inhibition of extracellular signal-regulated kinases and protein kinase C on the enhancing effects of inflammatory mediators on resurgent currents in rat dorsal root ganglion neurons. We found that the extracellular signal-regulated kinases inhibitor U0126 completely prevented the enhancing effects of the inflammatory mediators on both Tetrodotoxin-sensitive and Tetrodotoxin-resistant resurgent currents in both small and medium dorsal root ganglion neurons. U0126 substantially reduced repetitive firing in small dorsal root ganglion neurons exposed to inflammatory mediators, consistent with prevention of resurgent current amplitude increases. The protein kinase C inhibitor Bisindolylmaleimide I also showed attenuating effects on resurgent currents, although to a lesser extent compared to extracellular signal-regulated kinases inhibition. These results indicate a critical role of extracellular signal-regulated kinases signaling in modulating resurgent currents and membrane excitability in dorsal root ganglion neurons treated with inflammatory mediators. It is also suggested that targeting extracellular signal-regulated kinases-resurgent currents might be a useful strategy to reduce inflammatory pain

A precise CNOT gate in the presence of large fabrication induced variations of the exchange interaction strength

We demonstrate how using two-qubit composite rotations a high fidelity controlled-NOT (CNOT) gate can be constructed, even when the strength of the interaction between qubits is not accurately known. We focus on the exchange interaction oscillation in silicon based solid-state architectures with a Heisenberg Hamiltonian. This method easily applies to a general two-qubit Hamiltonian. We show how the robust CNOT gate can achieve a very high fidelity when a single application of the composite rotations is combined with a modest level of Hamiltonian characterisation. Operating the robust CNOT gate in a suitably characterised system means concatenation of the composite pulse is unnecessary, hence reducing operation time, and ensuring the gate operates below the threshold required for fault-tolerant quantum computation.Comment: 9 pages, 8 figure

Quantum dot-labelled polymer beads by suspension polymerisation

CdSe quantum dots with polymerisable ligands have been incorporated into polystyrene beads, via a suspension polymerisation reaction, as a first step towards the optical encoding of solid supports for application in solid phase organic chemistry

The Impact of Cloud-To-Ground Lightning Type on the Differences in Return Stroke Peak Current Over Land and Ocean

Natural cloud-to-ground (CG) lightning behaves differently over land and ocean. These differences likely reflect local variations in the speed at which storms develop over ocean, and are possibly contributed to by differences in the local aerosol composition. Earlier studies have reported statistically larger peak currents for negative CG first strokes over ocean than over land. This work focuses on differences in this relationship for first strokes, for subsequent strokes in existing channels to ground, and for subsequent strokes creating new ground contacts. This distinction will shed light on the mechanism responsible for the observed land:ocean differences, and can either support or refute the hypothesis that this difference is associated with the propagation of downward negative leaders in free space, driven by the vertical profile of electric field within and below the cloud. Results show that when compensated for detection threshold increases with increasing distance from land-based sensors, the distribution of estimated peak currents for subsequent strokes in existing (pre-ionized) channels to ground was indistinguishable from distributions for lightning that occurred inland, near shore, offshore, and in the distant ocean (similar to 200 km offshore), with median values ranging between 14.4 and 15.1 kA. Conversely, the population of first strokes over distant ocean had much higher peak currents than those that occurred inland (median values of 23.1 kA vs. 17.3 kA, respectively), when corrected for detection threshold. These findings are consistent with the field-profile hypothesis noted above since peak currents for return strokes due to downward leaders that establish new channels (first strokes) would be impacted the most by the vertical profile of electric field near the cloud base, whereas the peak current for strokes in previously-established channels should be far less dependent on the field profile.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Genetic risk of obesity as a modifier of associations between neighbourhood environment and body mass index. An observational study of 335 046 UK Biobank participants

Background There is growing recognition that recent global increases in obesity are the product of a complex interplay between genetic and environmental factors. However, in gene-environment studies of obesity, ‘environment’ usually refers to individual behavioural factors that influence energy balance, whereas more upstream environmental factors are overlooked. We examined gene-environment interactions between genetic risk of obesity and two neighbourhood characteristics likely to be associated with obesity (proximity to takeaway/ fast-food outlets and availability of physical activity facilities). Methods We used data from 335 046 adults aged 40–70 in the UK Biobank cohort to conduct a populationbased cross-sectional study of interactions between neighbourhood characteristics and genetic risk of obesity, in relation to body mass index (BMI). Proximity to a fast-food outlet was defined as distance from home address to nearest takeaway/fast-food outlet, and availability of physical activity facilities as the number of formal physical activity facilities within 1 km of home address. Genetic risk of obesity was operationalised by weighted Genetic Risk Scores of 91 or 69 single nucleotide polymorphisms (SNP), and by six individual SNPs considered separately. Multivariable, mixed-effects models with product terms for the gene-environment interactions were estimated. Results After accounting for likely confounding, the association between proximity to takeaway/fast-food outlets and BMI was stronger among those at increased genetic risk of obesity, with evidence of an interaction with polygenic risk scores (p=0.018 and p=0.028 for 69- SNP and 91-SNP scores, respectively) and in particular with a SNP linked to MC4R (p=0.009), a gene known to regulate food intake. We found very little evidence of geneenvironment interaction for the availability of physical activity facilities. Conclusions Individuals at an increased genetic risk of obesity may be more sensitive to exposure to the local fast-food environment. Ensuring that neighbourhood residential environments are designed to promote a healthy weight may be particularly important for those with greater genetic susceptibility to obesity

Health professional perspectives on lifestyle behaviour change in the paediatric hospital setting : a qualitative study

BACKGROUND: Research exists examining the challenges of delivering lifestyle behaviour change initiatives in practice. However, at present much of this research has been conducted with primary care health professionals, or in acute adult hospital settings. The purpose of this study was to identify barriers and facilitators associated with implementing routine lifestyle behaviour change brief advice into practice in an acute children’s hospital. METHODS: Thirty-three health professionals (nurses, junior doctors, allied health professionals and clinical support staff) from inpatient and outpatient departments at a UK children’s hospital were interviewed about their attitudes and beliefs towards supporting lifestyle behaviour change in hospital patients and their families. Responses were analysed using thematic framework analysis. RESULTS: Health professionals identified a range of barriers and facilitators to supporting lifestyle behaviour change in a children’s hospital. These included (1) personal experience of effectiveness, (2) constraints associated with the hospital environment, (3) appropriateness of advice delivery given the patient’s condition and care pathway and (4) job role priorities, and (5) perceived benefits of the advice given. Delivery of lifestyle behaviour change advice was often seen as an educational activity, rather than a behaviour change activity. CONCLUSION: Factors underpinning the successful delivery of routine lifestyle behaviour change support must be understood if this is to be implemented effectively in paediatric acute settings. This study reveals key areas where paediatric health professionals may need further support and training to achieve successful implementation

General criteria for the stability of uniaxially ordered states of Incommensurate-Commensurate Systems

Reconsidering the variational procedure for uniaxial systems modeled by continuous free energy functionals, we derive new general conditions for thermodynamic extrema. The utility of these conditions is briefly illustrated on the models for the classes I and II of incommensurate-commensurate systems.Comment: 5 pages, to be published in Phys. Rev. Let

Molecular mode-coupling theory applied to a liquid of diatomic molecules

We study the molecular mode coupling theory for a liquid of diatomic molecules. The equations for the critical tensorial nonergodicity parameters ${\bf F}_{ll'}^m(q)$ and the critical amplitudes of the $\beta$ - relaxation ${\bf H}_{ll'}^m(q)$ are solved up to a cut off $l_{co}$ = 2 without any further approximations. Here $l,m$ are indices of spherical harmonics. Contrary to previous studies, where additional approximations were applied, we find in agreement with simulations, that all molecular degrees of freedom vitrify at a single temperature $T_c$. The theoretical results for the non ergodicity parameters and the critical amplitudes are compared with those from simulations. The qualitative agreement is good for all molecular degrees of freedom. To study the influence of the cut off on the non ergodicity parameter, we also calculate the non ergodicity parameters for an upper cut off $l_{co}=4$. In addition we also propose a new method for the calculation of the critical nonergodicity parameterComment: 27 pages, 17 figure

An investigation into CLIL-related sections of EFL coursebooks : issues of CLIL inclusion in the publishing market

The current ELT global coursebook market has embraced CLIL as a weak form of bilingual education and an innovative component to include in General English coursebooks for EFL contexts. In this paper I investigate how CLIL is included in ELT coursebooks aimed at teenaged learners, available to teachers in Argentina. My study is based on the content analysis of four series which include a section advertised as CLIL-oriented. Results suggest that such sections are characterised by (1) little correlation between featured subject specific content and school curricula in L1, (2) oversimplification of contents, and (3) dominance of reading skills development and lower-order thinking tasks. Through this study, I argue that CLIL components become superficial supplements rather than a meaningful attempt to promote weak forms of bilingual education

Protein kinase C enhances human sodium channel hNav1.7 resurgent currents via a serine residue in the domain III-IV linker

Resurgent sodium currents likely play a role in modulating neuronal excitability. Here we studied whether protein kinase C (PKC) activation can increase resurgent currents produced by the human sodium channel hNav1.7. We found that a PKC agonist significantly enhanced hNav1.7-mediated resurgent currents and this was prevented by PKC antagonists. The enhancing effects were replicated by two phosphorylation-mimicking mutations and were prevented by a phosphorylation-deficient mutation at a conserved PKC phosphorylation site (Serine 1479). Our results suggest that PKC can increase sodium resurgent currents through phosphorylation of a conserved Serine residue located in the domain III-IV linker of sodium channels