Facile preparation of antibacterial, highly elastic silvered polyurethane nanofiber fabrics using silver carbamate and their dermal wound healing properties

In this study, polycarbonate diol/isosorbide-based antibacterial polyurethane nanofiber fabrics containing Ag nanoparticles were prepared by electrospinning process. Bio-based highly elastic polyurethane was prepared from hexamethylene diisocyanate and isosorbide/polycarbonate diol (8/2) by a simple one-shot bulk polymerization. Ag nanoparticles were formed using simple thermal reduction of silver 2-ethylhexylcarbamate at 120℃. The structural and morphological properties of polyurethane/Ag nanofibers were characterized by X-ray diffraction and scanning electron microscopy. The polyurethane nanofiber fabrics were flexible, with breaking strains from 355% to 950% under 7.28 to 23.1 MPa tensile stress. The antibacterial effects of the treated polyurethane/Ag fabrics against Staphylococcus aureus and methicillin resistant Staphylococcus aureus were examined and found to be excellent. Cell proliferation using the immortalized human keratinocyte HaCaT cell line was performed in order to determine cell viability in the presence of polyurethane and polyurethane/Ag fabrics, showing cytocompatiblility and a lack of toxicity

Using Genetic Variants to Assess the Relationship Between Circulating Lipids and Type 2 Diabetes

Journal ArticleResearch Support, Non-U.S. Gov'tCopyright © 2015 by the American Diabetes Association.This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db14-1710/-/DC1.The effects of dyslipidemia on the risk of type 2 diabetes (T2D) and related traits are not clear. We used regression models and 140 lipid-associated genetic variants to estimate associations between circulating HDL cholesterol (HDL-C), LDL cholesterol (LDL-C), and triglycerides and T2D and related traits. Each genetic test was corrected for effects of variants on the other two lipid types and surrogates of adiposity. We used the largest data sets available: 34,840 T2D case and 114,981 control subjects from the DIAGRAM (DIAbetes Genetics Replication And Meta-analysis) consortium and up to 133,010 individuals without diabetes for insulin secretion and sensitivity from the MAGIC (Meta-Analyses of Glucose and Insulin-related traits Consortium) and GENESIS (GENEticS of Insulin Sensitivity) studies. Eight of 21 associations between groups of variants and diabetes traits were significant at the nominal level, including those between genetically determined lower HDL-C (β = -0.12, P = 0.03) and T2D and genetically determined lower LDL-C (β = -0.21, P = 5 × 10(-6)) and T2D. Although some of these may represent causal associations, we discuss why caution must be used when using Mendelian randomization in the context of circulating lipid levels and diabetes traits. In conclusion, we found evidence of links between genetic variants associated with lipids and T2D, but deeper knowledge of the underlying genetic mechanisms of specific lipid variants is needed before drawing definite conclusions about causality based on Mendelian randomization methodology.Knut and Alice Wallenberg FoundationERCSwedish Research CouncilFredrik och Ingrid Thurings StiftelseSwedish Heart-Lung Foundationacknowledges Sydvästra Skånes DiabetesföreningNovo Nordisk FoundationUniversity of TartuEuropean Foundation for the Study of Diabetes New HorizonsAmerican Heart Associatio

Approximating Mexican highways with slime mould

Plasmodium of Physarum polycephalum is a single cell visible by unaided eye. During its foraging behavior the cell spans spatially distributed sources of nutrients with a protoplasmic network. Geometrical structure of the protoplasmic networks allows the plasmodium to optimize transport of nutrients between remote parts of its body. Assuming major Mexican cities are sources of nutrients how much structure of Physarum protoplasmic network correspond to structure of Mexican Federal highway network? To find an answer undertook a series of laboratory experiments with living Physarum polycephalum. We represent geographical locations of major cities by oat flakes, place a piece of plasmodium in Mexico city area, record the plasmodium's foraging behavior and extract topology of nutrient transport networks. Results of our experiments show that the protoplasmic network formed by Physarum is isomorphic, subject to limitations imposed, to a network of principle highways. Ideas and results of the paper may contribute towards future developments in bio-inspired road planning

Structural and functional characterization of Pseudomonas aeruginosa CupB chaperones

Pseudomonas aeruginosa, an important human pathogen, is estimated to be responsible for,10% of nosocomial infections worldwide. The pathogenesis of P. aeruginosa starts from its colonization in the damaged tissue or medical devices (e. g. catheters, prothesis and implanted heart valve etc.) facilitated by several extracellular adhesive factors including fimbrial pili. Several clusters containing fimbrial genes have been previously identified on the P. aeruginosa chromosome and named cup [1]. The assembly of the CupB pili is thought to be coordinated by two chaperones, CupB2 and CupB4. However, due to the lack of structural and biochemical data, their chaperone activities remain speculative. In this study, we report the 2.5 A crystal structure of P. aeruginosa CupB2. Based on the structure, we further tested the binding specificity of CupB2 and CupB4 towards CupB1 (the presumed major pilus subunit) and CupB6 (the putative adhesin) using limited trypsin digestion and strep-tactin pull-down assay. The structural and biochemical data suggest that CupB2 and CupB4 might play different, but not redundant, roles in CupB secretion. CupB2 is likely to be the chaperone of CupB1, and CupB4 could be the chaperone of CupB4:CupB5:CupB6, in which the interaction of CupB4 and CupB6 might be mediated via CupB5

Prediction of peptide and protein propensity for amyloid formation

Understanding which peptides and proteins have the potential to undergo amyloid formation and what driving forces are responsible for amyloid-like fiber formation and stabilization remains limited. This is mainly because proteins that can undergo structural changes, which lead to amyloid formation, are quite diverse and share no obvious sequence or structural homology, despite the structural similarity found in the fibrils. To address these issues, a novel approach based on recursive feature selection and feed-forward neural networks was undertaken to identify key features highly correlated with the self-assembly problem. This approach allowed the identification of seven physicochemical and biochemical properties of the amino acids highly associated with the self-assembly of peptides and proteins into amyloid-like fibrils (normalized frequency of β-sheet, normalized frequency of β-sheet from LG, weights for β-sheet at the window position of 1, isoelectric point, atom-based hydrophobic moment, helix termination parameter at position j+1 and ΔGº values for peptides extrapolated in 0 M urea). Moreover, these features enabled the development of a new predictor (available at http://cran.r-project.org/web/packages/appnn/index.html) capable of accurately and reliably predicting the amyloidogenic propensity from the polypeptide sequence alone with a prediction accuracy of 84.9 % against an external validation dataset of sequences with experimental in vitro, evidence of amyloid formation

Integrated Epigenome Profiling of Repressive Histone Modifications, DNA Methylation and Gene Expression in Normal and Malignant Urothelial Cells

Epigenetic regulation of gene expression is commonly altered in human cancer. We have observed alterations of DNA methylation and microRNA expression that reflect the biology of bladder cancer. This common disease arises by distinct pathways with low and high-grade differentiation. We hypothesized that epigenetic gene regulation reflects an interaction between histone and DNA modifications, and differences between normal and malignant urothelial cells represent carcinogenic events within bladder cancer. To test this we profiled two repressive histone modifications (H3K9m3 and H3K27m3) using ChIP-Seq, cytosine methylation using MeDIP and mRNA expression in normal and malignant urothelial cell lines. In genes with low expression we identified H3K27m3 and DNA methylation each in 20–30% of genes and both marks in 5% of genes. H3K9m3 was detected in 5–10% of genes but was not associated with overall expression. DNA methylation was more closely related to gene expression in malignant than normal cells. H3K27m3 was the epigenetic mark most specifically correlated to gene silencing. Our data suggest that urothelial carcinogenesis is accompanied by a loss of control of both DNA methylation and H3k27 methylation. From our observations we identified a panel of genes with cancer specific-epigenetic mediated aberrant expression including those with reported carcinogenic functions and members potentially mediating a positive epigenetic feedback loop. Pathway enrichment analysis revealed genes marked by H3K9m3 were involved with cell homeostasis, those marked by H3K27m3 mediated pro-carcinogenic processes and those marked with cytosine methylation were mixed in function. In 150 normal and malignant urothelial samples, our gene panel correctly estimated expression in 65% of its members. Hierarchical clustering revealed that this gene panel stratified samples according to the presence and phenotype of bladder cancer

Hematological profile of East African Short-Horn Zebu calves: From birth to 51 weeks of age

This paper is the first attempt to accurately describe the hematological parameters for any African breed of cattle, by capturing the changes in these parameters over the first 12 months of an animal’s life using a population based sample of calves reared under field conditions and natural disease challenge. Using a longitudinal study design, a stratified clustered random sample of newborn calves was recruited into the Infectious Diseases of East African Livestock (IDEAL) study and monitored at 5-weekly intervals until 51 weeks of age. The blood cell analysis performed at each visit included: packed cell volume; red cell count; red cell distribution width; mean corpuscular volume; mean corpuscular hemoglobin concentration; hemoglobin concentration; white cell count; absolute lymphocyte, eosinophil, monocyte, and neutrophil counts; platelet count; mean platelet volume; and total serum protein. The most significant age-related change in the red cell parameters was a rise in red cell count and hemoglobin concentration during the neonatal period. This is in contrast to what is reported for other ruminants, including European cattle breeds where the neonatal period is marked by a fall in the red cell parameters. There is a need to establish breed specific reference ranges for blood parameters for indigenous cattle breeds. The possible role of the postnatal rise in the red cell parameters in the adaptability to environmental constraints and innate disease resistance warrants further research into the dynamics of blood cell parameters of these breed

?2-Microglobulin Amyloid Fibril-Induced Membrane Disruption Is Enhanced by Endosomal Lipids and Acidic pH

Although the molecular mechanisms underlying the pathology of amyloidoses are not well understood, the interaction between amyloid proteins and cell membranes is thought to play a role in several amyloid diseases. Amyloid fibrils of ?2-microglobulin (?2m), associated with dialysis-related amyloidosis (DRA), have been shown to cause disruption of anionic lipid bilayers in vitro. However, the effect of lipid composition and the chemical environment in which ?2m-lipid interactions occur have not been investigated previously. Here we examine membrane damage resulting from the interaction of ?2m monomers and fibrils with lipid bilayers. Using dye release, tryptophan fluorescence quenching and fluorescence confocal microscopy assays we investigate the effect of anionic lipid composition and pH on the susceptibility of liposomes to fibril-induced membrane damage. We show that ?2m fibril-induced membrane disruption is modulated by anionic lipid composition and is enhanced by acidic pH. Most strikingly, the greatest degree of membrane disruption is observed for liposomes containing bis(monoacylglycero)phosphate (BMP) at acidic pH, conditions likely to reflect those encountered in the endocytic pathway. The results suggest that the interaction between ?2m fibrils and membranes of endosomal origin may play a role in the molecular mechanism of ?2m amyloid-associated osteoarticular tissue destruction in DRA

Interaction of enamel matrix proteins with human periodontal ligament cells

Dorothy Hodgkin Postgraduate Award for research studies (jointly funded by the Engineering and Physical Sciences Research Council, UK, and by Institut Straumann) and the Research Discretionary Funds of the Periodontology Unit, UCL Eastman Dental Institute. Financial support was also provided by the NIHR Comprehensive Biomedical Research Centre and by the WCU Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (No. R31-10069)