Preparation of Ni–YSZ thin and thick films on metallic interconnects as cell supports. Applications as anode for SOFC

In this work, we propose the preparation of a duplex anodic layer composed of both a thin (100 nm) and a thick film (10 lm) with Ni–YSZ material. The support of this anode is a metallic substrate, which is the interconnect of the SOFC unit cell. The metallic support limits the temperature of thermal treatment at 800 C to keep a good interconnect mechanical behaviour and to reduce corrosion. We have chosen to elaborate anodic coatings by sol–gel route coupled with dip-coating process, which are low cost techniques and allow working with moderate temperatures. Thin films are obtained by dipping interconnect substrate into a sol, and thick films into an optimized slurry. After thermal treatment at only 800 C, anodic coatings are adherent and homogeneous. Thin films have compact microstructures that confer ceramic protective barrier on metal surface. Further coatings of 10 lm thick are porous and constitute the active anodic material

Anthelmintic resistance to ivermectin and moxidectin in gastrointestinal nematodes of cattle in Europe

Anthelmintic resistance has been increasingly reported in cattle worldwide over the last decade, although reports from Europe are more limited. The objective of the present study was to evaluate the efficacy of injectable formulations of ivermectin and moxidectin at 0.2 mg per kg bodyweight against naturally acquired gastro-intestinal nematodes in cattle. A total of 753 animals on 40 farms were enrolled in Germany (12 farms), the UK (10 farms), Italy (10 farms), and France (8 farms). Animals were selected based on pre-treatment faecal egg counts and were allocated to one of the two treatment groups. Each treatment group consisted of between 7 and 10 animals. A post-treatment faecal egg count was performed 14 days (±2 days) after treatment. The observed percentage reduction was calculated for each treatment group based on the arithmetic mean faecal egg count before and after treatment. The resistance status was evaluated based on the reduction in arithmetic mean faecal egg count and both the lower and upper 95% confidence limits. A decreased efficacy was observed in half or more of the farms in Germany, France and the UK. For moxidectin, resistance was confirmed on 3 farms in France, and on 1 farm in Germany and the UK. For ivermectin, resistance was confirmed on 3 farms in the UK, and on 1 farm in Germany and France. The remaining farms with decreased efficacy were classified as having an inconclusive resistance status based on the available data. After treatment Cooperia spp. larvae were most frequently identified, though Ostertagia ostertagi was also found, in particular within the UK and Germany. The present study reports lower than expected efficacy for ivermectin and moxidectin (based on the reduction in egg excretion after treatment) on European cattle farms, with confirmed anthelmintic resistance on 12.5% of the farms

P120-Catenin Isoforms 1 and 3 Regulate Proliferation and Cell Cycle of Lung Cancer Cells via β-Catenin and Kaiso Respectively

<div><h3>Background</h3><p>The different mechanisms involved in p120-catenin (p120ctn) isoforms' 1/3 regulation of cell cycle progression are still not elucidated to date.</p> <h3>Methods and Findings</h3><p>We found that both cyclin D1 and cyclin E could be effectively restored by restitution of p120ctn-1A or p120ctn-3A in p120ctn depleted lung cancer cells. When the expression of cyclin D1 was blocked by co-transfection with siRNA-cyclin D1 in p120ctn depleted cells restoring p120ctn-1A or 3A, the expression of cyclin E was slightly decreased, not increased, implying that p120ctn isoforms 1 and 3 cannot up-regulate cyclin E directly but may do so through up-regulation of cyclin D1. Interestingly, overexpression of p120ctn-1A increased β-catenin and cyclin D1 expression, while co-transfection with siRNA targeting β-catenin abolishes the effect of p120ctn-1A on up-regulation of cyclin D1, suggesting a role of β-catenin in mediating p120ctn-1A's regulatory function on cyclin D1 expression. On the other hand, overexpression of p120ctn isoform 3A reduced nuclear Kaiso localization, thus decreasing the binding of Kaiso to KBS on the cyclin D1 promoter and thereby enhancing the expression of cyclin D1 gene by relieving the repressor effect of Kaiso. Because overexpressing NLS-p120ctn-3A (p120ctn-3A nuclear target localization plasmids) or inhibiting nuclear export of p120ctn-3 by Leptomycin B (LMB) caused translocation of Kaiso to the nucleus, it is plausible that the nuclear export of Kaiso is p120ctn-3-dependent.</p> <h3>Conclusions</h3><p>Our results suggest that p120ctn isoforms 1 and 3 up-regulate cyclin D1, and thereby cyclin E, resulting in the promotion of cell proliferation and cell cycle progression in lung cancer cells probably via different protein mediators, namely, β-catenin for isoform 1 and Kaiso, a negative transcriptional factor of cyclin D1, for isoform 3.</p> </div

Membrane Permeabilization by Oligomeric α-Synuclein: In Search of the Mechanism

Background: \ud The question of how the aggregation of the neuronal protein α-synuclein contributes to neuronal toxicity in Parkinson's disease has been the subject of intensive research over the past decade. Recently, attention has shifted from the amyloid fibrils to soluble oligomeric intermediates in the α-synuclein aggregation process. These oligomers are hypothesized to be cytotoxic and to permeabilize cellular membranes, possibly by forming pore-like complexes in the bilayer. Although the subject of α-synuclein oligomer-membrane interactions has attracted much attention, there is only limited evidence that supports the pore formation by α-synuclein oligomers. In addition the existing data are contradictory.\ud \ud Methodology/Principal Findings:\ud Here we have studied the mechanism of lipid bilayer disruption by a well-characterized α-synuclein oligomer species in detail using a number of in vitro bilayer systems and assays. Dye efflux from vesicles induced by oligomeric α-synuclein was found to be a fast all-or-none process. Individual vesicles swiftly lose their contents but overall vesicle morphology remains unaltered. A newly developed assay based on a dextran-coupled dye showed that non-equilibrium processes dominate the disruption of the vesicles. The membrane is highly permeable to solute influx directly after oligomer addition, after which membrane integrity is partly restored. The permeabilization of the membrane is possibly related to the intrinsic instability of the bilayer. Vesicles composed of negatively charged lipids, which are generally used for measuring α-synuclein-lipid interactions, were unstable to protein adsorption in general.\ud \ud Conclusions/Significance:\ud The dye efflux from negatively charged vesicles upon addition of α-synuclein has been hypothesized to occur through the formation of oligomeric membrane pores. However, our results show that the dye efflux characteristics are consistent with bilayer defects caused by membrane instability. These data shed new insights into potential mechanisms of toxicity of oligomeric α-synuclein species

Associations of familial risk factors with social fears and social phobia: evidence for the continuum hypothesis in social anxiety disorder?

We examined parental psychopathology and family environment in subthreshold and DSM-IV threshold conditions of social anxiety disorder (SAD) in a representative cohort sample of 1,395 adolescents. Offspring and parental psychopathology was assessed using the DIA-X/M-CIDI; recalled parental rearing and family functioning via questionnaire. Diagnostic interviews in parents were supplemented by family history reports from offspring. The cumulative lifetime incidence was 23.07% for symptomatic SAD, and 18.38 and 7.41% for subthreshold and threshold SAD, respectively. The specific parent-to-offspring association for SAD occurred for threshold SAD only. For subthreshold and threshold SAD similar associations were found with other parental anxiety disorders, depression and substance use disorders. Parental rearing behaviour, but not family functioning, was associated with offspring threshold SAD, and although less strong and less consistent, also with subthreshold SAD. Results suggest a continued graded relationship between familial risk factors and offspring SAD. Parental psychopathology and negative parental styles may be used defining high-risk groups to assign individuals with already subthreshold conditions of SAD to early intervention programs

Imaging the nanoscale organization of peptidoglycan in living Lactococcus lactis cells

Peptidoglycans provide bacterial cell walls with mechanical strength. The spatial organization of peptidoglycan has previously been difficult to study. Here, atomic force microscopy, together with cells carrying mutations in cell-wall polysaccharides, has allowed an in-depth study of these molecules

Cryptococcal Neuroradiological Lesions Correlate with Severity during Cryptococcal Meningoencephalitis in HIV-Positive Patients in the HAART Era

Cryptococcal meningoencephalitis has an overall global mortality rate of 20% in AIDS patients despite antifungals. There is a need for additional means of precise assessment of disease severity. We thus studied the radiological brain images available from 62 HIV-positive patients with cryptococcocal meningoencephalitis to analyse the brain lesions associated with cryptococcosis in relationship with disease severity, and the respective diagnostic contribution of magnetic resonance (MR) versus computed tomography (CT)

The Role of Alpha-Synuclein Oligomerization and Aggregation in Cellular and Animal Models of Parkinson’s Disease

α-synuclein (α-syn) is a synaptic protein in which four mutations (A53T, A30P, E46K and gene triplication) have been found to cause an autosomal dominant form of Parkinson’s disease (PD). It is also the major component of intraneuronal protein aggregates, designated as Lewy bodies (LBs), a prominent pathological hallmark of PD. How α-syn contributes to LB formation and PD is still not well-understood. It has been proposed that aggregation of α-syn contributes to the formation of LBs, which then leads to neurodegeneration in PD. However, studies have also suggested that aggregates formation is a protective mechanism against more toxic α-syn oligomers. In this study, we have generated α-syn mutants that have increased propensity to form aggregates by attaching a CL1 peptide to the C-terminal of α-syn. Data from our cellular study suggest an inverse correlation between cell viability and the amount of α-syn aggregates formed in the cells. In addition, our animal model of PD indicates that attachment of CL1 to α-syn enhanced its toxicity to dopaminergic neurons in an age-dependent manner and induced the formation of Lewy body-like α-syn aggregates in the substantia nigra. These results provide new insights into how α-syn-induced toxicity is related to its aggregation

Competition and parasitism in the native White Clawed Crayfish Austropotamobius pallipes and the invasive Signal Crayfish Pacifastacus leniusculus in the UK

Many crayfish species have been introduced to novel habitats worldwide, often threatening extinction of native species. Here we investigate competitive interactions and parasite infections in the native Austropotamobius pallipes and the invasive Pacifastacus leniusculus from single and mixed species populations in theUK. We found A. pallipes individuals to be significantly smaller in mixed compared to single species populations; conversely P. leniusculus individuals were larger in mixed than in single species populations. Our data provide no support for reproductive interference as a mechanism of competitive displacement and instead suggest competitive exclusion of A. pallipes from refuges by P. leniusculus leading to differential predation. We screened 52 P. leniusculus and 12 A. pallipes for microsporidian infection using PCR. We present the first molecular confirmation of Thelohania contejeani in the native A. pallipes; in addition, we provide the first evidence for T. contejeani in the invasive P. leniusculus. Three novel parasite sequenceswere also isolated fromP. leniusculus with an overall prevalence of microsporidian infection of 38% within this species; we discuss the identity of and the similarity between these three novel sequences. We also screened a subset of fifteen P. leniusculus and three A. pallipes for Aphanomyces astaci, the causative agent of crayfish plague and for the protistan crayfish parasite Psorospermium haeckeli. We found no evidence for infection by either agent in any of the crayfish screened. The high prevalence of microsporidian parasites and occurrence of shared T. contejeani infection lead us to propose that future studies should consider the impact of these parasites on native and invasive host fitness and their potential effects upon the dynamics of native-invader systems

Change in quality of life and their predictors in the long-term follow-up after group cognitive behavioral therapy for social anxiety disorder: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Social anxiety disorder (SAD) is one of the most common anxiety disorders. The efficacy of cognitive behaviour therapy (CBT) has been examined but to date its effects on Quality of Life (QoL) have not been appropriately evaluated especially in the long term.</p> <p>The study aimed to examine, in the long term, what aspects of Quality of Life (QoL) changed among social anxiety disorder (SAD) patients treated with group cognitive behaviour therapy (CBT) and what predictors at baseline were associated with QoL.</p> <p>Methods</p> <p>Outpatients diagnosed with SAD were enrolled into group CBT, and assessed at follow-ups for up to 12 months in a typical clinical setting. QoL was evaluated using the Short Form 36. Various aspects of SAD symptomatology were also assessed. Each of the QoL domains and scores on symptomatology were quantified and compared with those at baseline. Baseline predictors of QoL outcomes at follow-up were investigated.</p> <p>Results</p> <p>Fifty-seven outpatients were enrolled into group CBT for SAD, 48 completed the whole program, and 44 and 40 completed assessments at the 3-month and 12-month follow-ups, respectively. All aspects of SAD symptomatology and psychological subscales of the QoL showed statistically significant improvement throughout follow-ups for up to 12 months. In terms of social functioning, no statistically significant improvement was observed at either follow-up point except for post-treatment. No consistently significant pre-treatment predictors were observed.</p> <p>Conclusions</p> <p>After group CBT, SAD symptomatology and some aspects of QoL improved and this improvement was maintained for up to 12 months, but the social functioning domain did not prove any significant change statistically. Considering the limited effects of CBT on QoL, especially for social functioning, more powerful treatments are needed.</p