Lack of involvement of lipocortin 1 in dexamethasone suppression of IL-1 release

The annexin lipocortin 1 is reported to mediate some anti-inflammatory effects of glucocorticoids, but the mechanisms of this mediation are incompletely understood. The involvement of lipocortin 1 in glucocorticoid inhibition of monocyte interleukin 1β (IL-1β) release has been investigated. Treatment of peripheral blood monocytes with 2 μg/ml lipopolysaccharide potently increased IL–1β release (p = 0.001) and dexamethasone (10−7 M) significantly reduced both resting and stimulated IL-1β release (p = 0.009). A neutralizing monoclonal antibody to lipocortin 1 (0.5–50.0 μg/ml) was unable to inhibit this effect and recombinant lipocortin 1 (2 × 10−6 M) and 188aa lipocortin 1 fragment (10−8−10−6 M) had no effect. It is concluded that lipocortin 1 is not involved in the inhibition of monocyte IL-1β release by glucocorticoids

Differential modulation of annexin I binding sites on monocytes and neutrophils.

Specific binding sites for the anti-inflammatory protein annexin I have been detected on the surface of human monocytes and polymorphonuclear leukocytes (PMN). These binding sites are proteinaceous in nature and are sensitive to cleavage by the proteolytic enzymes trypsin, collagenase, elastase and cathepsin G. When monocytes and PMN were isolated independently from peripheral blood, only the monocytes exhibited constitutive annexin I binding. However PMN acquired the capacity to bind annexin I following co-culture with monocytes. PMN incubation with sodium azide, but not protease inhibitors, partially blocked this process. A similar increase in annexin I binding capacity was also detected in PMN following adhesion to endothelial monolayers. We propose that a juxtacrine activation rather than a cleavage-mediated transfer is involved in this process. Removal of annexin I binding sites from monocytes with elastase rendered monocytes functionally insensitive to full length annexin I or to the annexin I-derived pharmacophore, peptide Ac2-26, assessed as suppression of the respiratory burst. These data indicate that the annexin I binding site on phagocytic cells may have an important function in the feedback control of the inflammatory response and their loss through cleavage could potentiate such responses

Derivative spectroscopy and the continuous relaxation spectrum

Derivative spectroscopy is conventionally understood to be a collection of techniques for extracting fine structure from spectroscopic data by means of numerical differentiation. In this paper we extend the conventional interpretation of derivative spectroscopy with a view to recovering the continuous relaxation spectrum of a viscoelastic material from oscillatory shear data. To achieve this, the term “spectroscopic data” is allowed to include spectral data which have been severely broadened by the action of a strong low-pass filter. Consequently, a higher order of differentiation than is usually encountered in conventional derivative spectroscopy is required. However, by establishing a link between derivative spectroscopy and wavelet decomposition, high-order differentiation of oscillatory shear data can be achieved using specially constructed wavelet smoothing. This method of recovery is justified when the reciprocal of the Fourier transform of the filter function (convolution kernel) is an entire function, and is particularly powerful when the associated Maclaurin series converges rapidly. All derivatives are expressed algebraically in terms of scaling functions and wavelets of different scales, and the recovered relaxation spectrum is expressible in analytic form. An important feature of the method is that it facilitates local recovery of the spectrum, and is therefore appropriate for real scenarios where the oscillatory shear data is only available for a finite range of frequencies. We validate the method using synthetic data, but also demonstrate its use on real experimental data

J-band variability of M dwarfs in the WFCAM Transit Survey

We present an analysis of the photometric variability of M dwarfs in the Wide Field Camera (WFCAM) Transit Survey. Although periodic light-curve variability in low mass stars is generally dominated by photospheric star spot activity, M dwarf variability in the J band has not been as thoroughly investigated as at visible wavelengths. Spectral type estimates for a sample of over 200 000 objects are made using spectral type-colour relations, and over 9600 dwarfs (J 0.2 mag flaring event from an M4V star in our sample.Peer reviewe

Developing implementation research capacity: longitudinal evaluation of the King's College London Implementation Science Masterclass, 2014-2019.

BACKGROUND: Despite an increasing number of training opportunities in implementation science becoming available, the demand for training amongst researchers and practitioners is unmet. To address this training shortfall, we developed the King's College London 'Implementation Science Masterclass' (ISM), an innovative 2-day programme (and currently the largest of its kind in Europe), developed and delivered by an international faculty of implementation experts. METHODS: This paper describes the ISM and provides delegates' quantitative and qualitative evaluations (gathered through a survey at the end of the ISM) and faculty reflections over the period it has been running (2014-2019). RESULTS: Across the 6-year evaluation, a total of 501 delegates have attended the ISM, with numbers increasing yearly from 40 (in 2014) to 147 (in 2019). Delegates represent a diversity of backgrounds and 29 countries from across the world. The overall response rate for the delegate survey was 64.5% (323/501). Annually, the ISM has been rated 'highly' in terms of delegates' overall impression (92%), clear and relevant learning objectives (90% and 94%, respectively), the course duration (85%), pace (86%) and academic level 87%), and the support provided on the day (92%). Seventy-one percent of delegates reported the ISM would have an impact on how they approached their future work. Qualitative feedback revealed key strengths include the opportunities to meet with an international and diverse pool of experts and individuals working in the field, the interactive nature of the workshops and training sessions, and the breadth of topics and contexts covered. CONCLUSIONS: Yearly, the UK ISM has grown, both in size and in its international reach. Rated consistently favourably by delegates, the ISM helps to tackle current training demands from all those interested in learning and building their skills in implementation science. Evaluation of the ISM will continue to be an annual iterative process, reflective of changes in the evidence base and delegates changing needs as the field evolves

Liming impacts barley yield over a wide concentration range of soil exchangeable cations

Liming has widespread and significant impacts on soil processes and crop responses. The aim of this study was to describe the relationships between exchangeable cation concentrations in soil and the relative yield of spring barley. The hypothesis was that yield is restricted by the concentration of a single exchangeable cation in the soil. For simplicity, we focused on spring barley which was grown in nine years of a long-term experiment at two sites (Rothamsted and Woburn). Four liming rates were applied and in each year the relative yield (RY) and the concentrations of exchangeable cations were assessed. Liming had highly significant effects on the concentrations of most exchangeable cations, except for Cu and K. There were significant negative relationships (either linear or exponential) between the exchangeable concentrations of Mn, Cd, Cr, Al, Fe, Cu, Co, Zn and Ni in soil and soil pH. The relationships between RY and the concentrations of selected exchangeable cations (Mn, Ca and Al) were described well using log-logistic relationships. For these cations a significant site effect was probably due to fundamental differences in soil properties. At both sites the concentrations of exchangeable soil Al were excessive ([ 7.5 mg kg-1) and were most likely responsible for reduced barley yields (where RY B 0.5) with soil acidification. At Rothamsted barley yield was nonlimited (where RY C 1) at soil exchangeable Mn concentrations (up to 417 mg kg-1) greater than previously considered toxic, which requires further evaluation of critical Mn concentrations

Idylls of socialism : the Sarajevo Documentary School and the problem of the Bosnian sub-proletariat

This historical overview of the Sarajevo Documentary School considers the films, in the light of their recent re-emergence, as indicative of both the legacy of socialist realism (even in the context of Yugoslav media) and attempted social engineering in the Bosnia of the 1960s and 1970s. The argument is made that the documentaries, despite their questionable aesthetic status (in respect of cinma-vrit and ethnography) and problematic ideological strategies and attempted interventions, document a history and offer insights that counter the prevailing revisionist trends in the presentation of Eastern and Central European history

Cyprus' image—a sun and sea destination—as a detrimental factor to seasonal fluctuations. Exploration into motivational factors for holidaying in Cyprus

Cyprus is established as a summer destination. To aid the destination in developing its winter season as well, this research uses a qualitative inductive approach to explore the tourists’ current image of the island and their motivations of visiting it. The research indicates that the current image, which essentially portrays Cyprus as a sun-and-sea destination is thought to dissuade tourists from perceiving the island as a year-round destination. Nonetheless, increasing the pull factors of the destination through the development of unique special interest products can help in extending the tourism season as well as broaden its narrow image

Post-vaccine epidemiology of serotype 3 pneumococci identifies transformation inhibition through prophage-driven alteration of a non-coding RNA

Background: The respiratory pathogen Streptococcus pneumoniae (the pneumococcus) is a genetically diverse bacterium associated with over 101 immunologically distinct polysaccharide capsules (serotypes). Polysaccharide conjugate vaccines (PCVs) have successfully eliminated multiple targeted serotypes, yet the mucoid serotype 3 has persisted despite its inclusion in PCV13. This capsule type is predominantly associated with a single globally disseminated strain, GPSC12 (clonal complex 180).Methods: A genomic epidemiology study combined previous surveillance datasets of serotype 3 pneumococci to analyse the population structure, dynamics, and differences in rates of diversification within GPSC12 during the period of PCV introductions. Transcriptomic analyses, whole genome sequencing, mutagenesis, and electron microscopy were used to characterise the phenotypic impact of loci hypothesised to affect this strain's evolution.Results: GPSC12 was split into clades by a genomic analysis. Clade I, the most common, rarely underwent transformation, but was typically infected with the prophage phi OXC141. Prior to the introduction of PCV13, this Glade's composition shifted towards a phi OXC141-negative subpopulation in a systematically sampled UK collection. In the post-PCV13 era, more rapidly recombining non-Clade I isolates, also phi OXC141-negative, have risen in prevalence. The low in vitro transformation efficiency of a Clade I isolate could not be fully explained by the similar to 100-fold reduction attributable to the serotype 3 capsule. Accordingly, prophage phi OXC141 was found to modify csRNA3, a non-coding RNA that inhibits the induction of transformation. This alteration was identified in -30% of all pneumococci and was particularly common in the unusually clonal serotype 1 GPSC2 strain. RNA-seq and quantitative reverse transcriptase PCR experiments using a genetically tractable pneumococcus demonstrated the altered csRNA3 was more effective at inhibiting production of the competence-stimulating peptide pheromone. This resulted in a reduction in the induction of competence for transformation.Conclusion: This interference with the quorum sensing needed to induce competence reduces the risk of the prophage being deleted by homologous recombination. Hence the selfish prophage-driven alteration of a regulatory RNA limits cell-cell communication and horizontal gene transfer, complicating the interpretation of post-vaccine population dynamics