A Crucial Role of Flagellin in the Induction of Airway Mucus Production by Pseudomonas aeruginosa

Pseudomonas aeruginosa is an opportunistic pathogen involved in nosocomial infections. Flagellin is a P. aeruginosa virulence factor involved in host response to this pathogen. We examined the role of flagellin in P. aeruginosa-induced mucus secretion. Using a mouse model of pulmonary infection we showed that PAK, a wild type strain of P. aeruginosa, induced airway mucus secretion and mucin muc5ac expression at higher levels than its flagellin-deficient mutant (ΔFliC). PAK induced expression of MUC5AC and MUC2 in both human airway epithelial NCI-H292 cell line and in primary epithelial cells. In contrast, ΔFliC infection had lower to no effect on MUC5AC and MUC2 expressions. A purified P. aeruginosa flagellin induced MUC5AC expression in parallel to IL-8 secretion in NCI-H292 cells. Accordingly, ΔFliC mutant stimulated IL-8 secretion at significantly lower levels compared to PAK. Incubation of NCI-H292 cells with exogenous IL-8 induced MUC5AC expression and pre-incubation of these cells with an anti-IL-8 antibody abrogated flagellin-mediated MUC5AC expression. Silencing of TLR5 and Naip, siRNA inhibited both flagellin-induced MUC5AC expression and IL-8 secretion. Finally, inhibition of ERK abolished the expression of both PAK- and flagellin-induced MUC5AC. We conclude that: (i) flagellin is crucial in P. aeruginosa-induced mucus hyper-secretion through TLR5 and Naip pathways; (ii) this process is mediated by ERK and amplified by IL-8. Our findings help understand the mechanisms involved in mucus secretion during pulmonary infectious disease induced by P. aeruginosa, such as in cystic fibrosis

Prevalence of disability in a composite ≥75 year-old population in Spain: A screening survey based on the International Classification of Functioning

<p>Abstract</p> <p>Background</p> <p>The prevalence and predictors of functional status and disability of elderly people have been studied in several European countries including Spain. However, there has been no population-based study incorporating the International Classification of Functioning, Disability and Health (ICF) framework as the basis for assessing disability. The present study reports prevalence rates for mild, moderate, and severe/extreme disability by the domains of activities and participation of the ICF.</p> <p>Methods</p> <p>Nine populations surveyed in previous prevalence studies contributed probabilistic and geographically defined samples in June 2005. The study sample was composed of 503 subjects aged ≥75 years. We implemented a two-phase screening design using the MMSE and the World Health Organization-Disability Assessment Schedule 2^ndedition (WHO-DAS II, 12 items) as cognitive and disability screening tools, respectively. Participants scoring within the positive range of the disability screening were administered the full WHO-DAS II (36 items; score range: 0-100) assessing the following areas: Understanding and communication, Getting along with people, Life activities, Getting around, Participation in society, and Self-care. Each disability area assessed by WHO-DAS II (36 items) was reported according to the ICF severity ranges (No problem, 0-4; Mild disability, 5-24; Moderate disability, 25-49; Severe/Extreme disability, 50-100).</p> <p>Results</p> <p>The age-adjusted disability prevalence figures were: 39.17 ± 2.18%, 15.31 ± 1.61%, and 10.14 ± 1.35% for mild, moderate, and severe/extreme disability, respectively. Severe and extreme disability prevalence in mobility and life activities was three times higher than the average, and highest among women. Sex variations were minimal, although life activities for women of 85 years and over had more severe/extreme disability as compared to men (OR = 5.15 95% CI 3.19-8.32).</p> <p>Conclusions</p> <p>Disability is highly prevalent among the Spanish elderly. Sex- and age-specific variations of disability are associated with particular disability domains.</p

Tsunami hazards in the Catalan Coast, a low-intensity seismic activity area

The final publication is available at Springer via http://dx.doi.org/10.1007/s11069-017-2918-zThe potential impacts of tsunamis along the Catalan Coast (NW Mediterranean) are analysed using numerical modelling. The region is characterized by moderate to low seismic activity and by moderate- to low-magnitude earthquakes. However, the occurrence of historical strong earthquakes and the location of several active offshore faults in front of the coast suggest that the possibility of an earthquake-triggered tsunami is not negligible although of low probability. Up to five faults have been identified to generate tsunamis, being the highest associated possible seismic magnitudes of up to 7.6. Coastal flooding and port agitation are characterized using the Worst-case Credible Tsunami Scenario Analysis approach. The results show a multiple fault source contribution to tsunami hazard. The shelf dimensions and the existence of submerged canyons control the tsunami propagation. In wide shelves, waves travelling offshore may become trapped by refraction causing the wave energy to reach the coastline at some distance from the origin. The free surface water elevation increases at the head of the canyons due to the sharp depth gradients. The effects of potential tsunamis would be very harmful in low-lying coastal stretches, such as deltas, with a high population concentration, assets and infrastructures. The Ebro delta appears to be the most exposed coast, and about the 20% of the delta surface is prone to flooding due to its extremely low-lying nature. The activity at Barcelona port will be severely affected by inflow backflow current at the entrance of up to 2 m/s.Peer ReviewedPostprint (author's final draft

Phenomenology of a light gluon resonance in top-physics at Tevatron and LHC

We present a phenomenological analysis of the recent Tevatron results on the $t \bar t$ forward-backward asymmetry and invariant-mass spectrum assuming a new contribution from an s-channel gluon resonance with a mass in the range from 700 to 2500 GeV. In contrast to most of the previous works, this analysis shows that for masses below ~1 TeV resonant New Physics could accommodate the experimental data. In general, we find that axial-like couplings are preferred for light and top quark couplings, and that only top quark couples strongly to New Physics. We find that composite model scenarios arise naturally from only phenomenological analyses of the experimental results. We show that our results are compatible with recent LHC limits in dijet and $t \bar t$ production, and find some tension for large resonance mass ~2.5 TeV. We indicate as best observables for discriminating a relatively light new gluon a better resolution in CDF forward-backward asymmetry, as well as the $t \bar t$ charge asymmetry and invariant-mass spectrum at the LHC.Comment: 22 pages with 5 figure

BMP9 Protects Septal Neurons from Axotomy-Evoked Loss of Cholinergic Phenotype

Cholinergic projection from the septum to the hippocampus is crucial for normal cognitive function and degeneration of cells and nerve fibers within the septohippocampal pathway contributes to the pathophysiology of Alzheimer's disease. Bone morphogenetic protein (BMP) 9 is a cholinergic differentiating factor during development both in vivo and in vitro.To determine whether BMP9 could protect the adult cholinergic septohippocampal pathway from axotomy-evoked loss of the cholinergic phenotype, we performed unilateral fimbria-fornix transection in mice and treated them with a continuous intracerebroventricular infusion of BMP9 for six days. The number of choline acetyltransferase (CHAT)-positive cells was reduced by 50% in the medial septal nucleus ipsilateral to the lesion as compared to the intact, contralateral side, and BMP9 infusion prevented this loss in a dose-dependent manner. Moreover, BMP9 prevented most of the decline of hippocampal acetylcholine levels ipsilateral to the lesion, and markedly increased CHAT, choline transporter CHT, NGF receptors p75 (NGFR-p75) and TrkA (NTRK1), and NGF protein content in both the lesioned and unlesioned hippocampi. In addition, BMP9 infusion reduced bilaterally hippocampal levels of basic FGF (FGF2) protein.These data indicate that BMP9 administration can prevent lesion-evoked impairment of the cholinergic septohippocampal neurons in adult mice and, by inducing NGF, establishes a trophic environment for these cells

Insulin and IGF1 signalling pathways in human astrocytes <i>in vitro</i> and <i>in vivo</i>; characterisation, subcellular localisation and modulation of the receptors.

Background The insulin/IGF1 signalling (IIS) pathways are involved in longevity regulation and are dysregulated in neurons in Alzheimer’s disease (AD). We previously showed downregulation in IIS gene expression in astrocytes with AD-neuropathology progression, but IIS in astrocytes remains poorly understood. We therefore examined the IIS pathway in human astrocytes and developed models to reduce IIS at the level of the insulin or the IGF1 receptor (IGF1R). Results We determined IIS was present and functional in human astrocytes by immunoblotting and showed astrocytes express the insulin receptor (IR)-B isoform of Ir. Immunocytochemistry and cell fractionation followed by western blotting revealed the phosphorylation status of insulin receptor substrate (IRS1) affects its subcellular localisation. To validate IRS1 expression patterns observed in culture, expression of key pathway components was assessed on post-mortem AD and control tissue using immunohistochemistry. Insulin signalling was impaired in cultured astrocytes by treatment with insulin + fructose and resulted in decreased IR and Akt phosphorylation (pAkt S473). A monoclonal antibody against IGF1R (MAB391) induced degradation of IGF1R receptor with an associated decrease in downstream pAkt S473. Neither treatment affected cell growth or viability as measured by MTT and Cyquant® assays or GFAP immunoreactivity. Discussion IIS is functional in astrocytes. IR-B is expressed in astrocytes which differs from the pattern in neurons, and may be important in differential susceptibility of astrocytes and neurons to insulin resistance. The variable presence of IRS1 in the nucleus, dependent on phosphorylation pattern, suggests the function of signalling molecules is not confined to cytoplasmic cascades. Down-regulation of IR and IGF1R, achieved by insulin + fructose and monoclonal antibody treatments, results in decreased downstream signalling, though the lack of effect on viability suggests that astrocytes can compensate for changes in single pathways. Changes in signalling in astrocytes, as well as in neurons, may be important in ageing and neurodegeneration

International entrepreneurship in SMEs: a study of influencing factors in the textile industry

The final publication is available at Springer via http://dx.doi.org/10.1007/s11365-012-0242-3International entrepreneurship is an incipient research area with a rapidly increasing body of knowledge and contributions. An important part of this literature has focused on the analysis of the contributing factors to IE development. From these studies, this work attempts to analyse and validate through an integrative model the effect on this construct in SME of some of the main factors proposed by the literature such as Skills and Competences, Attitude and Proactiveness, Creativity and Innovation, Networking, Employees and Activity. To proceed with this aim, we conducted an empirical research focused on 174 textile SME in Spain. The results obtained confirm a positive relationship between the studied factors and the IE development. 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Seroprevalence of 34 Human Papillomavirus Types in the German General Population

The natural history of infections with many human papillomavirus (HPV) types is poorly understood. Here, we describe for the first time the age- and sex-dependent antibody prevalence for 29 cutaneous and five mucosal HPV types from 15 species within five phylogenetic genera (alpha, beta, gamma, mu, nu) in a general population. Sera from 1,797 German adults and children (758 males and 1,039 females) between 1 and 82 years (median 37 years) were analysed for antibodies to the major capsid protein L1 by Luminex-based multiplex serology. The first substantial HPV antibody reactions observed already in children and young adults are those to cutaneous types of the genera nu (HPV 41) and mu (HPV 1, 63). The antibody prevalence to mucosal high-risk types, most prominently HPV 16, was elevated after puberty in women but not in men and peaked between 25 and 34 years. Antibodies to beta and gamma papillomaviruses (PV) were rare in children and increased homogeneously with age, with prevalence peaks at 40 and 60 years in women and 50 and 70 years in men. Antibodies to cutaneous alpha PV showed a heterogeneous age distribution. In summary, these data suggest three major seroprevalence patterns for HPV of phylogenetically distinct genera: antibodies to mu and nu skin PV appear early in life, those to mucosal alpha PV in women after puberty, and antibodies to beta as well as to gamma skin PV accumulate later in life