Response of airway epithelial cells to double-stranded RNA in an allergic environment.

BACKGROUND: Respiratory viral infections are the most common trigger of acute exacerbations in patients with allergic asthma. The anti-viral response of airway epithelial cells (AEC) may be impaired in asthmatics, while cytokines produced by AEC may drive the inflammatory response. We investigated whether AEC cultured in the presence of Th2 cytokines associated with an allergic environment exhibited altered responses to double-stranded RNA, a virus-like stimulus. METHODS: We undertook preliminary studies using the MLE-12 cell line derived from mouse distal respiratory epithelial cells, then confirmed and extended our findings using low-passage human AEC. Cells were cultured in the absence or presence of the Th2 cytokines IL-4 and IL-13 for 48 hours, then stimulated with poly I:C for 4 hours. Expression of relevant anti-viral response and cytokine genes was assessed by quantitative real-time PCR. Secretion of cytokine proteins was assessed by immunoassay. RESULTS: Following stimulation with poly I:C, MLE-12 cells pre-treated with Th2 cytokines exhibited significantly higher levels of expression of mRNA for the cytokine genes Cxcl10 and Cxcl11, as well as a trend towards increased expression of Cxcl9 and Il6. Expression of anti-viral response genes was mostly unchanged, although Stat1, Ifit1 and Ifitm3 were significantly increased in Th2 cytokine pre-treated cells. Human AEC pre-treated with IL-4 and IL-13, then stimulated with poly I:C, similarly exhibited significantly higher expression of IL8, CXCL9, CXCL10, CXCL11 and CCL5 genes. In parallel, there was significantly increased secretion of CXCL8 and CCL5, as well as a trend towards increased secretion of CXCL10 and IL-6. Again, expression of anti-viral response genes was not decreased. Rather, there was significantly enhanced expression of mRNA for type III interferons, RNA helicases and other interferon-stimulated genes. CONCLUSION: The Th2 cytokine environment appears to promote increased production of pro-inflammatory chemokines by AEC in response to double-stranded RNA, which could help explain the exaggerated inflammatory response to respiratory viral infection in allergic asthmatics. However, any impairment of anti-viral host defences in asthmatics appears unlikely to be a consequence of Th2 cytokine-induced downregulation of the expression of viral response genes by AEC

Statistical correlation for the composite Boson

It is well known that the particles in a beam of Boson obeying Bose-Einstein statistics tend to cluster (bunching effect), while the particles in a degenerate beam of Fermion obeying Fermi-Dirac statistics expel each other (anti-bunching effect). Here we investigate, for the first time, the statistical correlation effect for the composite Boson, which is formed from a spin singlet entangled electron pair. By using nonequilibrium Green's function technique, we obtain a positive cross correlation for this kind of the composite Boson when the external voltage is smaller than the gap energy, which demonstrates that a spin singlet entangled electron pair looks like a composite Boson. In the larger voltage limit, the cross correlation becomes negative due to the contribution of the quasiparticles. At large voltages, the oscillation between Fermionic and Bosonic behavior of cross correlation is also observed in the strong coupling regime as one changes the position of the resonant levels. Our result can be easily tested in a three-terminal normal-superconductor-superconductor (N-S-S) hybrid mesoscopic system

Managing plagiarism in programming assignments with blended assessment and randomisation.

Plagiarism is a common concern for coursework in many situations, particularly where electronic solutions can be provided e.g. computer programs, and leads to unreliability of assessment. Written exams are often used to try to deal with this, and to increase reliability, but at the expense of validity. One solution, outlined in this paper, is to randomise the work that is set for students so that it is very unlikely that any two students will be working on exactly the same problem set. This also helps to address the issue of students trying to outsource their work by paying external people to complete their assignments for them. We examine the effectiveness of this approach and others (including blended assessment) by analysing the spread of similarity scores across four different introductory programming assignments to find the natural similarity i.e. the level of similarity that could reasonably occur without plagiarism. The results of the study indicate that divergent assessment (having more than one possible solution) as opposed to convergent assessment (only one solution) is the dominant factor in natural similarity. A key area for further work is to apply the analysis to a larger sample of programming assignments to better understand the impact of different features of the assignment design on natural similarity and hence the detection of plagiarism

Kinesin-3 mediated axonal delivery of presynaptic neurexin stabilizes dendritic spines and postsynaptic components

The functional properties of neural circuits are defined by the patterns of synaptic connections between their partnering neurons, but the mechanisms that stabilize circuit connectivity are poorly understood. We systemically examined this question at synapses onto newly characterized dendritic spines of C. elegans GABAergic motor neurons. We show that the presynaptic adhesion protein neurexin/NRX-1 is required for stabilization of postsynaptic structure. We find that early postsynaptic developmental events proceed without a strict requirement for synaptic activity and are not disrupted by deletion of neurexin/nrx-1. However, in the absence of presynaptic NRX-1, dendritic spines and receptor clusters become destabilized and collapse prior to adulthood. We demonstrate that NRX-1 delivery to presynaptic terminals is dependent on kinesin-3/UNC-104 and show that ongoing UNC-104 function is required for postsynaptic maintenance in mature animals. By defining the dynamics and temporal order of synapse formation and maintenance events in vivo, we describe a mechanism for stabilizing mature circuit connectivity through neurexin-based adhesion

Pillared two-dimensional metal-organic frameworks based on a lower-rim acid appended calix[4]arene

Solvothermal reactions of the lower-rim functionalized diacid calix[4]arene 25,27-bis(methoxycarboxylic acid)-26,28-dihydroxy-4-tert-butylcalix[4]arene (LH₂) with Zn(NO₃)₂•6H₂O and the dipyridyl ligands 4,4/-bipyridyl (4,4/-bipy), 1,2-di(4-pyridyl)ethylene (DPE) or 4,4/-azopyridyl (4,4/-azopy) afforded a series of 2-D structures of the formulae {[Zn(4,4/-bipy)(L)]•2¼DEF}n (1), {[Zn₂(L)(DPE)]•DEF}n (2) and {[Zn(OH₂)₂(L)(4,4/-azopy)]•DEF}n (3) (DEF = diethylformamide)

CHEMICAL CHARACTERIZATION AND ANTIMICROBIAL ACTIVITY OF HYDROETHANOLIC CRUDE EXTRACT OF EUGENIA FLORIDA DC (MYRTACEAE) LEAVES

Objective: The present study aimed to characterize and quantify the total phenolics, flavonoids and tannins in a hydroethanolic crude extract (70% (v/v) (EB)) of the leaves of E. florida DC, as well as to evaluate the antimicrobial activity of the extract against different species of micro-organisms.Methods: EB was characterized using a mass spectrometer equipped with a direct insertion device for in-stream injection (FIA). Quantitative analyses of major compounds were carried out by spectrophotometry. In addition, we evaluated the sensitivity profiles of different strains of yeast and bacteria against different concentrations of EB.Results: The classes found were in agreement with those described in the literature: flavonoids, tannins, phenolic acids and saponins. EB showed levels of phenolic compounds, flavonoids and tannins equal to 25.82 mg gallic acid equivalents per gram of extract (EAG/g), 8.42 mg quercetin equivalents per gram of extract (EQ/g) and 7.30 mg tannic acid equivalents per gram of extract (AT/g), respectively. In the analysis of antimicrobial activity, EB was more active against yeasts but was not effective against the bacteria used in the test.Conclusion: We can conclude that E. florida DC has antimicrobial potential, due to the presence of bioactive secondary metabolites.Keywords: Phenolics, Micro-organisms, Mass spectrometer, Yeasts, Bacteria, PotentialÂ