Sialylation of campylobacter jejuni lipo-oligosaccharides: impact on phagocytosis and cytokine production in mice

<p>Background: Guillain-Barré syndrome (GBS) is a post-infectious polyradiculoneuropathy, frequently associated with antecedent Campylobacter jejuni (C. jejuni) infection. The presence of sialic acid on C. jejuni lipo-oligosaccharide (LOS) is considered a risk factor for development of GBS as it crucially determines the structural homology between LOS and gangliosides, explaining the induction of cross-reactive neurotoxic antibodies. Sialylated C. jejuni are recognised by TLR4 and sialoadhesin; however, the functional implications of these interactions in vivo are unknown.</p> <p>Methodology/Principal Findings: In this study we investigated the effects of bacterial sialylation on phagocytosis and cytokine secretion by mouse myeloid cells in vitro and in vivo. Using fluorescently labelled GM1a/GD1a ganglioside-mimicking C. jejuni strains and corresponding (Cst-II-mutant) control strains lacking sialic acid, we show that sialylated C. jejuni was more efficiently phagocytosed in vitro by BM-MΦ, but not by BM-DC. In addition, LOS sialylation increased the production of IL-10, IL-6 and IFN-β by both BM-MΦ and BM-DC. Subsequent in vivo experiments revealed that sialylation augmented the deposition of fluorescent bacteria in splenic DC, but not macrophages. In addition, sialylation significantly amplified the production of type I interferons, which was independent of pDC.</p> <p>Conclusions/Significance: These results identify novel immune stimulatory effects of C. jejuni sialylation, which may be important in inducing cross-reactive humoral responses that cause GBS</p&gt

The ρ-meson light-cone distribution amplitudes from lattice QCD

We present the results of a lattice study of the normalization constants and second moments of the light-cone distribution amplitudes of longitudinally and transversely polarized $\rho$ mesons. The calculation is performed using two flavors of dynamical clover fermions at lattice spacings between $0.060\,\text{fm}$ and $0.081\,\text{fm}$, different lattice volumes up to $m_\pi L = 6.7$ and pion masses down to $m_\pi=150\,\text{MeV}$. Bare lattice results are renormalized non-perturbatively using a variant of the RI'-MOM scheme and converted to the $\overline{\text{MS}}$ scheme. The necessary conversion coefficients, which are not available in the literature, are calculated. The chiral extrapolation for the relevant decay constants is worked out in detail. We obtain for the ratio of the tensor and vector coupling constants $f_\rho^T/f_\rho^{\vphantom{T}} = 0.629(8)$ and the values of the second Gegenbauer moments $a_2^\parallel = 0.132(27)$ and $a_2^\perp = 0.101(22)$ at the scale $\mu = 2\,\text{GeV}$ for the longitudinally and transversely polarized $\rho$ mesons, respectively. The errors include the statistical uncertainty and estimates of the systematics arising from renormalization. Discretization errors cannot be estimated reliably and are not included. In this calculation the possibility of $\rho\to\pi\pi$ decay at the smaller pion masses is not taken into account

Neural field models with threshold noise

The original neural field model of Wilson and Cowan is often interpreted as the averaged behaviour of a network of switch like neural elements with a distribution of switch thresholds, giving rise to the classic sigmoidal population firing-rate function so prevalent in large scale neuronal modelling. In this paper we explore the effects of such threshold noise without recourse to averaging and show that spatial correlations can have a strong effect on the behaviour of waves and patterns in continuum models. Moreover, for a prescribed spatial covariance function we explore the differences in behaviour that can emerge when the underlying stationary distribution is changed from Gaussian to non-Gaussian. For travelling front solutions, in a system with exponentially decaying spatial interactions, we make use of an interface approach to calculate the instantaneous wave speed analytically as a series expansion in the noise strength. From this we find that, for weak noise, the spatially averaged speed depends only on the choice of covariance function and not on the shape of the stationary distribution. For a system with a Mexican-hat spatial connectivity we further find that noise can induce localised bump solutions, and using an interface stability argument show that there can be multiple stable solution branches

A rare case of sarcoidosis involving the middle turbinates: an incidental diagnosis

BACKGROUND: Sarcoidosis is a chronic, systemic granulomatous disease of unknown etiology that features noncaseating granulomas in many body regions. Sinonasal involvement is rare but is also suspected to be underreported. CASE PRESENTATION: We present the case of a 39-year-old woman who was incidentally diagnosed with isolated sarcoidosis involving the middle turbinates. Histopathologic examination of resected concha bullosa material and an extensive panel of diagnostic tests revealed a diagnosis of isolated sarcoidosis. Since no systemic manifestations were detected, topical corticosteroid (nasal spray) was administered in the postoperative period. Throughout the 12 months after surgery, the patient remained free of symptoms and all nasal endoscopy examinations were normal. CONCLUSION: Although isolated nasal involvement of sarcoidosis is rare, otorhinolaryngologists should consider this condition in a differential diagnosis for sinonasal complaints

Bisexual women's understandings of social marginalisation: 'The heterosexuals don't understand US but nor do the lesbians'

Drawing on interviews with 20 self-identified bisexual women, this paper contributes to the limited psychological literature on bisexual women by exploring their experiences of social marginalisation. These (mainly white and middle class) British bisexual women reported that they did not feel at home in either lesbian or lesbian, gay, bisexual and transgender communities, nor in the wider (heteronormative) society. They identified a number of understandings - bisexuality as a temporary phase on the path to a fully realised lesbian or heterosexual identity and bisexuals as immature, confused, greedy, untrustworthy, highly sexual and incapable of monogamy - which they reported as arising from lesbian, gay, bisexual and transgender communities and the wider society. The women refuted these accounts which they stated did not reflect their experiences of bisexual identity and which positioned bisexuality as invisible and invalid. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav

Microbial ligand costimulation drives neutrophilic steroid-refractory asthma

Funding: The authors thank the Wellcome Trust (102705) and the Universities of Aberdeen and Cape Town for funding. This research was also supported, in part, by National Institutes of Health GM53522 and GM083016 to DLW. KF and BNL are funded by the Fonds Wetenschappelijk Onderzoek, BNL is the recipient of an European Research Commission consolidator grant and participates in the European Union FP7 programs EUBIOPRED and MedALL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Assessing the genetic association between vitamin B6 metabolism and genetic generalized epilepsy

Altered vitamin B6 metabolism due to pathogenic variants in the gene PNPO causes early onset epileptic encephalopathy, which can be treated with high doses of vitamin B6. We recently reported that single nucleotide polymorphisms (SNPs) that influence PNPO expression in the brain are associated with genetic generalized epilepsy (GGE). However, it is not known whether any of these GGE-associated SNPs influence vitamin B6 metabolite levels. Such an influence would suggest that vitamin B6 could play a role in GGE therapy. Here, we performed genome-wide association studies (GWAS) to assess the influence of GGE associated genetic variants on measures of vitamin B6 metabolism in blood plasma in 2232 healthy individuals. We also asked if SNPs that influence vitamin B6 were associated with GGE in 3122 affected individuals and 20,244 controls. Our GWAS of vitamin B6 metabolites reproduced a previous association and found a novel genome-wide significant locus. The SNPs in these loci were not associated with GGE. We found that 84 GGE-associated SNPs influence expression levels of PNPO in the brain as well as in blood. However, these SNPs were not associated with vitamin B6 metabolism in plasma. By leveraging polygenic risk scoring (PRS), we found suggestive evidence of higher catabolism and lower levels of the active and transport forms of vitamin B6 in GGE, although these findings require further replication

BounceBack™ capsules for reduction of DOMS after eccentric exercise: a randomized, double-blind, placebo-controlled, crossover pilot study

<p>Abstract</p> <p>Background</p> <p>Delayed onset muscle soreness (DOMS) is muscle pain and discomfort experienced approximately one to three days after exercise. DOMS is thought to be a result of microscopic muscle fiber tears that occur more commonly after eccentric exercise rather than concentric exercise. This study sought to test the efficacy of a proprietary dietary supplement, BounceBack™, to alleviate the severity of DOMS after standardized eccentric exercise.</p> <p>Methods</p> <p>The study was a randomized, double-blind, placebo-controlled, crossover study. Ten healthy community-dwelling untrained subjects, ranging in age from 18–45 years, were enrolled. Mean differences within and between groups were assessed inferentially at each data collection time-point using t-tests for all outcome measures.</p> <p>Results</p> <p>In this controlled pilot study, intake of BounceBack™ capsules for 30 days resulted in a significant reduction in standardized measures of pain and tenderness post-eccentric exercise compared to the placebo group. There were trends towards reductions in plasma indicators of inflammation (high sensitivity C-reactive protein) and muscle damage (creatine phosphokinase and myoglobin).</p> <p>Conclusion</p> <p>BounceBack™ capsules were able to significantly reduce standardized measures of pain and tenderness at several post-eccentric exercise time points in comparison to placebo. The differences in the serological markers of DOMS, while not statistically significant, appear to support the clinical findings. The product appears to have a good safety profile and further study with a larger sample size is warranted based on the current results.</p