Polyaniline nanoparticles for sensing applications.

Conducting polymers are being widely employed in the manufacture of nanostructured sensors due to breakthroughs in the development of sophisticated nano-sized forms. One of the most attractive conducting polymers is polyaniline (PANI) due to its interesting electrical, electrochemical and optical properties, such as air stability and simple acid/base doping/dedoping chemistry. However, the fact that aniline is a carcinogenic monomer, its insolubility in common solvents and the acidic conditions required to the most conductive form of PANI are made its commercial application very difficult so far. The synthesis of PANI nanoparticles using dodecylbenzenesulphonic acid (DBSA) as both dopant and surfactant have allowed the use of this polymer in aqueous media, improving its processability. The additional use of ammonium persulphate (APS) as an oxidant together with DBSA during chemical PANI polymerization have led to the creation of a spherical PANI nanoparticle aqueous dispersion. Such dispersion can be deposited onto the electrodes by means of traditional methods, such as drop coating, or using more sophisticated techniques, such as inkjet printing. The application of PANI nanoparticles inkjet printed onto carbon paste screen-printed electrodes for ascorbic acid sensing is shown in the present wor

The parasite cytokine mimic <i>Hp</i>-TGM potently replicates the regulatory effects of TGF-β on murine CD4+ T cells

Transforming growth factor‐beta (TGF‐β) family proteins mediate many vital biological functions in growth, development and regulation of the immune system. TGF‐β itself controls immune homeostasis and inflammation, including conversion of naïve CD4+ T cells into Foxp3+ regulatory T cells (Tregs) in the presence of IL‐2 and T cell receptor ligands. The helminth parasite Heligmosomoides polygyrus exploits this pathway through a structurally novel TGF‐β mimic (Hp‐TGM), which binds to mammalian TGF‐β receptors and induces Tregs. Here, we performed detailed comparisons of Hp‐TGM with mammalian TGF‐β. Compared to TGF‐β, Hp‐TGM induced greater numbers of Foxp3+ Tregs (iTregs), with more intense Foxp3 expression. Both ligands upregulated Treg functional markers CD73, CD103 and PD‐L1, but Hp‐TGM induced significantly higher CD39 expression than did TGF‐β. Interestingly, in contrast to canonical TGF‐β signalling through Smad2/3, Hp‐TGM stimulation was slower and more sustained. Gene expression profiles induced by TGF‐β and Hp‐TGM were remarkably similar, and both types of iTregs suppressed T cell responses in vitro and EAE‐driven inflammation in vivo. In vitro, both types of iTregs were equally stable under inflammatory conditions, but Hp‐TGM‐induced iTregs were more stable in vivo during DSS‐induced colitis, with greater retention of Foxp3 expression and lower conversion to a ROR‐γt+ phenotype. Altogether, results from this study suggest that the parasite cytokine mimic, Hp‐TGM, may deliver a qualitatively different signal to CD4+ T cells with downstream consequences for the long‐term stability of iTregs. These data highlight the potential of Hp‐TGM as a new modulator of T cell responses in vitro and in vivo

Amperometric separation-free immunosensor for real-time environmental monitoring

Immunoanalytical techniques have found widespread use due to the characteristics of specificity and wide applicability for many analytes, from large polymer antigens, to simple haptens, and even single atoms. Electrochemical sensors offer benefits of technical simplicity, speed and convenience via direct transduction to electronic equipment. Together, these two systems offer the possibility of a convenient, ubiquitous assay technique with high selectivity. However, they are still not widely used, mainly due to the complexity of the associated immunoassay methodologies. A separation-free immunoanalytical technique is described here, which has allowed for the analysis of atrazine in real time and in both quasi-equilibrium and stirred batch configurations. It illustrated that determinations as low as 0.13mM (28 ppb) could be made using equilibrium incubation with an analytical range of 0.1–10mM. Measurements could be made between 1 and 10 mM within several minutes using a real-time, stirred batch method. This system offers the potential for fast, simple, cost-effective biosensors for the analysis of many substances of environmental, biomedical and pharmaceutical concern

Anti-DLL4 VNAR targeted nanoparticles for targeting of both tumour and tumour associated vasculature

Acknowledgements The authors acknowledge the Engineering and Physical Sciences Research Council (EPSRC) (S3802ASA) and the generous support of the Martin Family Foundation for funding the Ph.D. studentships of P. S. and A. L., respectively. This work was also partially funded through a US-Ireland R&D Partnership grant awarded by HSCNI (STL/5010/14), Medical Research Council UK (MC_PC_15013), and the Biotechnology and Biological Sciences Research Council (BBSRC) (BB/R009112/1).Peer reviewedPublisher PD

Induction of stable human FOXP3⁺ Tregs by a parasite-derived TGF-β mimic

Immune homeostasis in the intestine is tightly controlled by FOXP3 + regulatory T cells (Tregs), defects of which are linked to the development of chronic conditions, such as inflammatory bowel disease (IBD). As a mechanism of immune evasion, several species of intestinal parasites boost Treg activity. The parasite Heligmosomoides polygyrus is known to secrete a molecule (Hp-TGM) that mimics the ability of TGF-β to induce FOXP3 expression in CD4 + T cells. The study aimed to investigate whether Hp-TGM could induce human FOXP3 + Tregs as a potential therapeutic approach for inflammatory diseases. CD4 + T cells from healthy volunteers were expanded in the presence of Hp-TGM or TGF-β. Treg induction was measured by flow cytometric detection of FOXP3 and other Treg markers, such as CD25 and CTLA-4. Epigenetic changes were detected using ChIP-Seq and pyrosequencing of FOXP3. Treg phenotype stability was assessed following inflammatory cytokine challenge and Treg function was evaluated by cellular co-culture suppression assays and cytometric bead arrays for secreted cytokines. Hp-TGM efficiently induced FOXP3 expression (&gt; 60%), in addition to CD25 and CTLA-4, and caused epigenetic modification of the FOXP3 locus to a greater extent than TGF-β. Hp-TGM-induced Tregs had superior suppressive function compared with TGF-β-induced Tregs, and retained their phenotype following exposure to inflammatory cytokines. Furthermore, Hp-TGM induced a Treg-like phenotype in in vivo differentiated Th1 and Th17 cells, indicating its potential to re-program memory cells to enhance immune tolerance. These data indicate Hp-TGM has potential to be used to generate stable human FOXP3 + Tregs to treat IBD and other inflammatory diseases. </p

Macrophage-specific responses to human -and animal- adapted tubercle bacilli reveal pathogen and host factors driving multinucleated cell formation

The Mycobacterium tuberculosis complex (MTBC) is a group of related pathogens that cause tuberculosis (TB) in mammals. MTBC species are distinguished by their ability to sustain in distinct host populations. While Mycobacterium bovis (Mbv) sustains transmission cycles in cattle and wild animals and causes zoonotic TB, M. tuberculosis (Mtb) affects human populations and seldom causes disease in cattle. The host and pathogen determinants underlying host tropism between MTBC species are still unknown. Macrophages are the main host cell that encounters mycobacteria upon initial infection, and we hypothesised that early interactions between the macrophage and mycobacteria influence species-specific disease outcome. To identify factors that contribute to host tropism, we analysed blood-derived primary human and bovine macrophages (hMϕ or bMϕ, respectively) infected with Mbv and Mtb. We show that Mbv and Mtb reside in different cellular compartments and differentially replicate in hMϕ whereas both Mbv and Mtb efficiently replicate in bMϕ. Specifically, we show that out of the four infection combinations, only the infection of bMϕ with Mbv promoted the formation of multinucleated giant cells (MNGCs), a hallmark of tuberculous granulomas. Mechanistically, we demonstrate that both MPB70 from Mbv and extracellular vesicles released by Mbv-infected bMϕ promote macrophage multinucleation. Importantly, we extended our in vitro studies to show that granulomas from Mbv-infected but not Mtb-infected cattle contained higher numbers of MNGCs. Our findings implicate MNGC formation in the contrasting pathology between Mtb and Mbv for the bovine host and identify MPB70 from Mbv and extracellular vesicles from bMϕ as mediators of this process

Factors that potentially influence successful weight loss for adults with intellectual disabilities: a qualitative comparison

Background: People with intellectual disabilities are more at risk of obesity than the general population. Emerging literature indicates that multicomponent interventions are most effective, however, individual results are variable and little research exists as to why this is the case. Methods: Focus groups were conducted to explore lived experiences between two groups of adults with intellectual disabilities; an overweight group (n= 6) and a group identified as successful in losing weight (n= 6). Similarities and differences were explored across four domains. Transcripts were produced and analysed using Theoretical Thematic Analysis. Results: Similarities included service centre supports, basic food knowledge and issues restricting independence. The successful weight loss group had also internalised health messages, engaged with external reinforcement programmes, responded to positive feedback and demonstrated healthier dietary habits. Conclusion: Weight management interventions would benefit from understanding the influence that internalisation of health messages, effective reinforcement systems and positive feedback can have on supporting the adoption of healthier habits.The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: This research was supported by funding from the charity RESPECT and the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement no. PCOFUND-GA-2013-608728. Additional funding for PhD research was provided by Department of Education and Learning (DEL).peer-reviewe

The impact of donor and recipient common clinical and genetic variation on estimated glomerular filtration rate in a European renal transplant population

Genetic variation across the HLA is known to influence renal‐transplant outcome. However, the impact of genetic variation beyond the HLA is less clear. We tested the association of common genetic variation and clinical characteristics, from both the donor and recipient, with post‐transplant eGFR at different time‐points, out to 5‐years post‐transplantation. We conducted GWAS meta‐analyses across 10,844 donors and recipients from five European ancestry cohorts. We also analysed the impact of polygenic risk scores (PRS), calculated using genetic variants associated with non‐transplant eGFR, on post‐transplant eGFR. PRS calculated using the recipient genotype alone, as well as combined donor and recipient genotypes were significantly associated with eGFR at 1‐year post‐transplant. 32% of the variability in eGFR at 1‐year post‐transplant was explained by our model containing clinical covariates (including weights for death/graft‐failure), principal components and combined donor‐recipient PRS, with 0.3% contributed by the PRS. No individual genetic variant was significantly associated with eGFR post‐transplant in the GWAS. This is the first study to examine PRS, composed of variants that impact kidney function in the general population, in a post‐transplant context. Despite PRS being a significant predictor of eGFR post‐transplant, the effect size of common genetic factors is limited compared to clinical variables

A functional definition to distinguish ponds from lakes and wetlands

Ponds are often identified by their small size and shallow depths, but the lack of a universal evidence-based definition hampers science and weakens legal protection. Here, we compile existing pond definitions, compare ecosystem metrics (e.g., metabolism, nutrient concentrations, and gas fluxes) among ponds, wetlands, and lakes, and propose an evidence-based pond definition. Compiled definitions often mentioned surface area and depth, but were largely qualitative and variable. Government legislation rarely defined ponds, despite commonly using the term. Ponds, as defined in published studies, varied in origin and hydroperiod and were often distinct from lakes and wetlands in water chemistry. We also compared how ecosystem metrics related to three variables often seen in waterbody definitions: waterbody size, maximum depth, and emergent vegetation cover. Most ecosystem metrics (e.g., water chemistry, gas fluxes, and metabolism) exhibited nonlinear relationships with these variables, with average threshold changes at 3.7 ± 1.8 ha (median: 1.5 ha) in surface area, 5.8 ± 2.5 m (median: 5.2 m) in depth, and 13.4 ± 6.3% (median: 8.2%) emergent vegetation cover. We use this evidence and prior definitions to define ponds as waterbodies that are small (< 5 ha), shallow (< 5 m), with < 30% emergent vegetation and we highlight areas for further study near these boundaries. This definition will inform the science, policy, and management of globally abundant and ecologically significant pond ecosystems.Fil: Richardson, David C.. State University of New York at New Paltz; Estados UnidosFil: Holgerson, Meredith A.. Cornell University; Estados UnidosFil: Farragher, Matthew J.. University of Maine; Estados UnidosFil: Hoffman, Kathryn K.. No especifíca;Fil: King, Katelyn B. S.. Michigan State University; Estados UnidosFil: Alfonso, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto Argentino de Oceanografía. Universidad Nacional del Sur. Instituto Argentino de Oceanografía; ArgentinaFil: Andersen, Mikkel R.. No especifíca;Fil: Cheruveil, Kendra Spence. Michigan State University; Estados UnidosFil: Coleman, Kristen A.. University of York; Reino UnidoFil: Farruggia, Mary Jade. University of California at Davis; Estados UnidosFil: Fernandez, Rocio Luz. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Hondula, Kelly L.. No especifíca;Fil: López Moreira Mazacotte, Gregorio A.. Leibniz - Institute of Freshwater Ecology and Inland Fisheries; AlemaniaFil: Paul, Katherine. No especifíca;Fil: Peierls, Benjamin L.. No especifíca;Fil: Rabaey, Joseph S.. University of Minnesota; Estados UnidosFil: Sadro, Steven. University of California at Davis; Estados UnidosFil: Sánchez, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Smyth, Robyn L.. No especifíca;Fil: Sweetman, Jon N.. State University of Pennsylvania; Estados Unido