Functionalization of PLLA with Polymer Brushes to Trigger the Assembly of Fibronectin into Nanonetworks

[EN] Poly-l-lactic acid (PLLA) has been used as a biodegradable polymer for many years; the key characteristics of this polymer make it a versatile and useful resource for regenerative medicine. However, it is not inherently bioactive. Thus, here, a novel process is presented to functionalize PLLA surfaces with poly(ethyl acrylate) (PEA) brushes to provide biological functionality through PEA's ability to induce spontaneous organization of the extracellular matrix component fibronectin (FN) into physiological-like nanofibrils. This process allows control of surface biofunctionality while maintaining PLLA bulk properties (i.e., degradation profile, mechanical strength). The new approach is based on surface-initiated atomic transfer radical polymerization, which achieves a molecularly thin coating of PEA on top of the underlying PLLA. Beside surface characterization via atomic force microscopy, X-ray photoelectron spectroscopy and water contact angle to measure PEA grafting, the biological activity of this surface modification is investigated. PEA brushes trigger FN organization into nanofibrils, which retain their ability to enhance adhesion and differentiation of C2C12 cells. The results demonstrate the potential of this technology to engineer controlled microenvironments to tune cell fate via biologically active surface modification of an otherwise bioinert biodegradable polymer, gaining wide use in tissue engineering applications.The authors acknowledge the EPSRC (EP/P001114/1) and MRC (MR/S005412/1) funding. The authors also acknowledge the EPSRC funding as part of the Doctoral Training Centre EP/F500424/1. This work was also funded by a grant from the UK Regenerative Medicine Platform. X-ray photoelectron spectroscopy was conducted by the National EPSRC XPS Users' Service (NEXUS), Newcastle.Sprott, MR.; Ferrer, G.; Dalby, MJ.; Salmerón Sánchez, M.; Cantini, M. (2019). Functionalization of PLLA with Polymer Brushes to Trigger the Assembly of Fibronectin into Nanonetworks. Advanced Healthcare Materials (Online). 8(3):1-12. https://doi.org/10.1002/adhm.201801469S11283A. J. Rincon Lasprilla G. A. Rueda Martinez B. H. Lunelli J. E. Jaimes Figueroa A. L. Jardini R. Maciel Filho Chem. Eng. Trans 2011 985Khan, F., Tanaka, M., & Ahmad, S. R. (2015). Fabrication of polymeric biomaterials: a strategy for tissue engineering and medical devices. Journal of Materials Chemistry B, 3(42), 8224-8249. doi:10.1039/c5tb01370dXu, F. J., Yang, X. C., Li, C. Y., & Yang, W. T. (2011). Functionalized Polylactide Film Surfaces via Surface-Initiated ATRP. Macromolecules, 44(7), 2371-2377. doi:10.1021/ma200160hKhan, F., & Tanaka, M. (2017). Designing Smart Biomaterials for Tissue Engineering. 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The electromagnetic nucleon form-factors data are studied with artificial feed forward neural networks. As a result the unbiased model-independent form-factor parametrizations are evaluated together with uncertainties. The Bayesian approach for the neural networks is adapted for chi2 error-like function and applied to the data analysis. The sequence of the feed forward neural networks with one hidden layer of units is considered. The given neural network represents a particular form-factor parametrization. The so-called evidence (the measure of how much the data favor given statistical model) is computed with the Bayesian framework and it is used to determine the best form factor parametrization.Comment: The revised version is divided into 4 sections. The discussion of the prior assumptions is added. The manuscript contains 4 new figures and 2 new tables (32 pages, 15 figures, 2 tables

Low-lying levels in F-15 and the shell model potential for drip-line nuclei

Journals published by the American Physical Society can be found at http://publish.aps.org/The ground and first excited states in F-15 were studied in resonant elastic scattering using the thick (CH4) gas target method in inverse kinematics with a separated O-14 beam. An analysis of the excitation functions of the elastic scattering was carried out with the potential model. The quantum numbers 1/2(+) (ground state) and 5/2(+) (first excited state) were assigned to the lowest two states in F-15. Also, the widths and the proton decay energies of the unbound levels were obtained. The analysis of the data indicates that a large diffuseness is needed in the Woods-Saxon potential in order to describe single-particle features in drip-line nuclei

Study protocol to investigate the effect of a lifestyle intervention on body weight, psychological health status and risk factors associated with disease recurrence in women recovering from breast cancer treatment

Background Breast cancer survivors often encounter physiological and psychological problems related to their diagnosis and treatment that can influence long-term prognosis. The aim of this research is to investigate the effects of a lifestyle intervention on body weight and psychological well-being in women recovering from breast cancer treatment, and to determine the relationship between changes in these variables and biomarkers associated with disease recurrence and survival. Methods/design Following ethical approval, a total of 100 patients will be randomly assigned to a lifestyle intervention (incorporating dietary energy restriction in conjunction with aerobic exercise training) or normal care control group. Patients randomised to the dietary and exercise intervention will be given individualised healthy eating dietary advice and written information and attend moderate intensity aerobic exercise sessions on three to five days per week for a period of 24 weeks. The aim of this strategy is to induce a steady weight loss of up to 0.5 Kg each week. In addition, the overall quality of the diet will be examined with a view to (i) reducing the dietary intake of fat to ~25% of the total calories, (ii) eating at least 5 portions of fruit and vegetables a day, (iii) increasing the intake of fibre and reducing refined carbohydrates, and (iv) taking moderate amounts of alcohol. Outcome measures will include body weight and body composition, psychological health status (stress and depression), cardiorespiratory fitness and quality of life. In addition, biomarkers associated with disease recurrence, including stress hormones, estrogen status, inflammatory markers and indices of innate and adaptive immune function will be monitored. Discussion This research will provide valuable information on the effectiveness of a practical, easily implemented lifestyle intervention for evoking positive effects on body weight and psychological well-being, two important factors that can influence long-term prognosis in breast cancer survivors. However, the added value of the study is that it will also evaluate the effects of the lifestyle intervention on a range of biomarkers associated with disease recurrence and survival. Considered together, the results should improve our understanding of the potential role that lifestyle-modifiable factors could play in saving or prolonging lives

PRNP variation in UK sporadic and variant Creutzfeldt Jakob disease highlights genetic risk factors and a novel non-synonymous polymorphism

<p>Abstract</p> <p>Background</p> <p>Genetic analysis of the human prion protein gene (<it>PRNP</it>) in suspect cases of Creutzfeldt-Jakob disease (CJD) is necessary for accurate diagnosis and case classification. Previous publications on the genetic variation at the <it>PRNP </it>locus have highlighted the presence of numerous polymorphisms, in addition to the well recognised one at codon 129, with significant variability between geographically distinct populations. It is therefore of interest to consider their influence on susceptibility or the clinico-pathological disease phenotype. This study aimed to characterise the frequency and effect of <it>PRNP </it>open reading frame polymorphisms other than codon 129 in both disease and control samples sourced from the United Kingdom population.</p> <p>Methods</p> <p>DNA was extracted from blood samples and genetic data obtained by full sequence analysis of the prion protein gene or by restriction fragment length polymorphism analysis using restriction enzymes specific to the gene polymorphism under investigation.</p> <p>Results</p> <p>147 of 166 confirmed cases of variant CJD (vCJD) in the UK have had <it>PRNP </it>codon 129 genotyping and all are methionine homozygous at codon 129; 118 have had full <it>PRNP </it>gene sequencing. Of the latter, 5 cases have shown other polymorphic loci: at codon 219 (2, 1.69%), at codon 202 (2, 1.69%), and a 24 bp deletion in the octapeptide repeat region (1, 0.85%). E219K and D202D were not found in sporadic CJD (sCJD) cases and therefore may represent genetic risk factors for vCJD.</p> <p>Genetic analysis of 309 confirmed UK sCJD patients showed codon 129 genotype frequencies of MM: 59.5% (n = 184), MV: 21.4% (n = 66), and VV: 19.1% (n = 59). Thirteen (4.2%) had the A117A polymorphism, one of which also had the P68P polymorphism, four (1.3%) had a 24 bp deletion, and a single patient had a novel missense variation at codon 167. As the phenotype of this latter case is similar to sCJD and in the absence of a family history of CJD, it is unknown whether this is a form of genetic CJD, or simply a neutral polymorphism.</p> <p>Conclusions</p> <p>This analysis of <it>PRNP </it>genetic variation in UK CJD patients is the first to show a comprehensive comparison with healthy individuals (n = 970) from the same population, who were genotyped for the three most common variations (codon 129, codon 117, and 24 bp deletion). These latter two genetic variations were equally frequent in UK sCJD or vCJD cases and a normal (healthy blood donor) UK population.</p