Functionalization of Surfaces with Nisin in a Polyethylene Oxide Brush Layer

Infections in hospitals account for over 100,000 deaths per year. These infections occur at the hospital from complications following bacterial adhesion to intravenous catheters, coronary stents and other implanted devices. Another common problem is protein adsorption to the surface of the device and subsequent blood clotting. Methods for combating these issues have been previously studied using antimicrobial coatings consisting of a tri‐block polymer with a hydrophobic base and two hydrophilic tails called Pluronic® F108 and an antimicrobial agent, nisin; however studies have not been conducted to determine how long such coatings are effective. Experiments were designed to test the long term efficacy of an F108 coated, nisin loaded surface for killing the Gram positive bacteria, Pediococcus pentosaceus. The overall experimentation, consisting of aging nisin‐coated microspheres for selected periods of time, followed by assaying bioactivity to determine nisin effectiveness, lasted 28 days, with samples taken from the microsphere suspensions once each week. These samples were plated on MRS agar plates and P. pentosaceus was allowed to grow for 48 hours, after which the colony forming units were counted for each sample. The F108‐coated, nisin loaded layers showed greater activity retention in comparison to layers prepared with nisin in the absence of F108, but only in the final week of the study

Adsorption, structural alteration and elution of peptides at pendant PEO layers

An experimentally based, quantitative understanding of the entrapment and function of small peptides within PEO brush layers does not currently exist. Earlier work provided a rationale for expecting that an ordered, compact peptide will enter the PEO phase more readily than a peptide of similar size that adopts a less ordered, less compact form, and that amphiphilicity will promote peptide retention within the hydrophobic region of the PEO brush. Here we more deliberately describe criteria for peptide integration and structural change within the PEO brush, and discuss the reversibility of peptide entrapment with changing solvent conditions. For this purpose, circular dichroism (CD) was used to record the adsorption and conformational changes of (amphiphilic) WLBU2 and (non-amphiphilic) polyarginine peptides at uncoated (hydrophobic) and PEO-coated silica nanoparticles. Peptide conformation was controlled between disordered and α-helical forms by varying the concentration of perchlorate ion. We show an initially more ordered (α-helical) structure promotes peptide adsorption into the PEO layer. Further, a partially helical peptide undergoes an increase in helicity after entry, likely due to concomitant loss of capacity for peptide-solvent hydrogen bonding. Peptide interaction with the PEO chains resulted in entrapment and conformational change that was irreversible to elution with changing solution conditions in the case of the amphiphilic peptide. In contrast, the adsorption and conformational change of the non-amphiphilic peptide was reversible. These results indicate that responsive drug delivery systems based on peptide-loaded PEO layers can be controlled by modulation of solution conditions and peptide amphiphilicity.Keywords: circular dichroism (CD), cationic amphiphilic peptides (CAPs), polyarginine, PEO brush, peptide integration, WLBU

Concentration effects on peptide elution from pendant PEO layers

In earlier work, we have provided direction for development of responsive drug delivery systems based on modulation of structure and amphiphilicity of bioactive peptides entrapped within pendant polyethylene oxide (PEO) brush layers. Amphiphilicity promotes retention of the peptides within the hydrophobic inner region of the PEO brush layer. In this work, we describe the effects of peptide surface density on the conformational changes caused by peptide-peptide interactions, and show that this phenomenon substantially affects the rate and extent of peptide elution from PEO brush layers. Three cationic peptides were used in this study: the arginine-rich amphiphilic peptide WLBU2, the chemically identical but scrambled peptide S-WLBU2, and the non-amphiphilic homopolymer poly-L-arginine (PLR). Circular dichroism (CD) was used to evaluate surface density effects on the structure of these peptides at uncoated (hydrophobic) and PEO-coated silica nanoparticles. UV spectroscopy and a quartz crystal microbalance with dissipation monitoring (QCM-D) were used to quantify changes in the extent of peptide elution caused by those conformational changes. For amphiphilic peptides at sufficiently high surface density, peptide-peptide interactions result in conformational changes which compromise their resistance to elution. In contrast, elution of a non-amphiphilic peptide is substantially independent of its surface density, presumably due to the absence of peptide-peptide interactions. The results presented here provide a strategy to control the rate and extent of release of bioactive peptides from PEO layers, based on modulation of their amphiphilicity and surface density.Keywords: α-Helix, PEO brush, Cationic amphiphilic peptides, Polyarginine, WLBU2, Coiled-coils, Circular dichroism (CD), Peptide elutio

The nature of delayed dream incorporation (‘dream-lag effect’): Personally significant events persist, but not major daily activities or concerns

Incorporation of details from waking life events into rapid eye movement (REM) sleep dreams has been found to be highest on the 2 nights after, and then 5–7 nights after, the event. These are termed, respectively, the day‐residue and dream‐lag effects. This study is the first to categorize types of waking life experiences and compare their incorporation into dreams across multiple successive nights. Thirty‐eight participants completed a daily diary each evening and a dream diary each morning for 14 days. In the daily diary, three categories of experiences were reported: major daily activities (MDAs), personally significant events (PSEs) and major concerns (MCs). After the 14‐day period each participant identified the correspondence between items in their daily diaries and subsequent dream reports. The day‐residue and dream‐lag effects were found for the incorporation of PSEs into dreams (effect sizes of .33 and .27, respectively), but only for participants (n = 19) who had a below‐median total number of correspondences between daily diary items and dream reports (termed “low‐incorporators” as opposed to “high‐incorporators”). Neither the day‐residue or dream‐lag effects were found for MDAs or MCs. This U‐shaped timescale of incorporation of events from daily life into dreams has been proposed to reflect REM sleep‐dependent memory consolidation, possibly related to emotional memory processing. This study had a larger sample size of dreams than any dream‐lag study hitherto with trained participants. Coupled with previous successful replications, there is thus substantial evidence supporting the dream‐lag effect and further explorations of its mechanism, including its neural underpinnings, are warranted

Critical animal and media studies: Expanding the understanding of oppression in communication research

Critical and communication studies have traditionally neglected the oppression conducted by humans towards other animals. However, our (mis)treatment of other animals is the result of public consent supported by a morally speciesist-anthropocentric system of values. Speciesism or anthroparchy, as much as any other mainstream ideologies, feeds the media and at the same time is perpetuated by them. The goal of this article is to remedy this neglect by introducing the subdiscipline of Critical Animal and Media Studies. Critical Animal and Media Studies takes inspiration both from critical animal studies – which is so far the most consolidated critical field of research in the social sciences addressing our exploitation of other animals – and from the normative-moral stance rooted in the cornerstones of traditional critical media studies. The authors argue that the Critical Animal and Media Studies approach is an unavoidable step forward for critical media and communication studies to engage with the expanded circle of concerns of contemporary ethical thinking

A vertically discretised canopy description for ORCHIDEE (SVN r2290) and the modifications to the energy, water and carbon fluxes

Since 70% of global forests are managed and forests impact the global carbon cycle and the energy exchange with the overlying atmosphere, forest management has the potential to mitigate climate change. Yet, none of the land surface models used in Earth system models, and therefore none of today’s predictions of future climate, account for the interactions between climate and forest management. We addressed this gap in modelling capability by developing and parametrizing a version of the land surface model ORCHIDEE to simulate the biogeochemical and biophysical effects of forest management. The most significant changes between the new branch called ORCHIDEE-CAN (SVN r2290) and the trunk version of ORCHIDEE (SVN r2243) are the allometric-based allocation of carbon to leaf, root, wood, fruit and reserve pools; the transmittance, absorbance and reflectance of radiation within the canopy; and the vertical discretisation of the energy budget calculations. In addition, conceptual changes were introduced towards a better process representation for the interaction of radiation with snow, the hydraulic architecture of plants, the representation of forest management and a numerical solution for the photosynthesis formalism of Farquhar, von Caemmerer and Berry. For consistency reasons, these changes were extensively linked throughout the code. Parametrization was revisited after introducing twelve new parameter sets that represent specific tree species or genera rather than a group of often distantly related or even unrelated species, as is the case in widely used plant functional types. Performance of the new model was compared against the trunk and validated against independent spatially explicit data for basal area, tree height, canopy strucure, GPP, albedo and evapotranspiration over Europe. For all tested variables ORCHIDEE-CAN outperformed the trunk regarding its ability to reproduce large-scale spatial patterns as well as their inter-annual variability over Europe. Depending on the data stream, ORCHIDEE-CAN had a 67% to 92% chance to reproduce the spatial and temporal variability of the validation data.JRC.H.5-Land Resources Managemen

Software Citation Checklist for Developers

This document provides a minimal, generic checklist that developers of software (either open or closed source) used in research can use to ensure they are following good practice around software citation. This will help developers get credit for the software they create, and improve transparency, reproducibility, and reuse

Modelling the impact of improving screening and treatment of chronic hepatitis C virus infection on future hepatocellular carcinoma rates and liver-related mortality.

BACKGROUND: The societal, clinical and economic burden imposed by the complications of chronic hepatitis C virus (HCV) infection - including cirrhosis and hepatocellular carcinoma (HCC) - is expected to increase over the coming decades. However, new therapies may improve sustained virological response (SVR) rates and shorten treatment duration. This study aimed to estimate the future burden of HCV-related disease in England if current management strategies remain the same and the impact of increasing diagnosis and treatment of HCV as new therapies become available. METHODS: A previously published model was adapted for England using published literature and government reports, and validated through an iterative process of three meetings of HCV experts. The impact of increasing diagnosis and treatment of HCV as new therapies become available was modelled and compared to the base-case scenario of continuing current management strategies. To assess the 'best case' clinical benefit of new therapies, the number of patients treated was increased by a total of 115% by 2018. RESULTS: In the base-case scenario, total viraemic (HCV RNA-positive) cases of HCV in England will decrease from 144,000 in 2013 to 76,300 in 2030. However, due to the slow progression of chronic HCV, the number of individuals with cirrhosis, decompensated cirrhosis and HCC will continue to increase over this period. The model suggests that the 'best case' substantially reduces HCV-related hepatic disease and HCV-related liver mortality by 2020 compared to the base-case scenario. The number of HCV-related HCC cases would decrease 50% by 2020 and the number progressing from infection to decompensated cirrhosis would decline by 65%. Therefore, compared to projections of current practices, increasing treatment numbers by 115% by 2018 would reduce HCV-related mortality by 50% by 2020. CONCLUSIONS: This analysis suggests that with current treatment practices the number of patients developing HCV-related cirrhosis, decompensated cirrhosis and HCC will increase substantially, with HCV-related liver deaths likely to double by 2030. However, increasing diagnosis and treatment rates could optimise the reduction in the burden of disease produced by the new therapies, potentially halving HCV-related liver mortality and HCV-related HCC by 2020

Assembly and Development of the Pseudomonas aeruginosa Biofilm Matrix

Virtually all cells living in multicellular structures such as tissues and organs are encased in an extracellular matrix. One of the most important features of a biofilm is the extracellular polymeric substance that functions as a matrix, holding bacterial cells together. Yet very little is known about how the matrix forms or how matrix components encase bacteria during biofilm development. Pseudomonas aeruginosa forms environmentally and clinically relevant biofilms and is a paradigm organism for the study of biofilms. The extracellular polymeric substance of P. aeruginosa biofilms is an ill-defined mix of polysaccharides, nucleic acids, and proteins. Here, we directly visualize the product of the polysaccharide synthesis locus (Psl exopolysaccharide) at different stages of biofilm development. During attachment, Psl is anchored on the cell surface in a helical pattern. This promotes cell–cell interactions and assembly of a matrix, which holds bacteria in the biofilm and on the surface. Chemical dissociation of Psl from the bacterial surface disrupted the Psl matrix as well as the biofilm structure. During biofilm maturation, Psl accumulates on the periphery of 3-D-structured microcolonies, resulting in a Psl matrix-free cavity in the microcolony center. At the dispersion stage, swimming cells appear in this matrix cavity. Dead cells and extracellular DNA (eDNA) are also concentrated in the Psl matrix-free area. Deletion of genes that control cell death and autolysis affects the formation of the matrix cavity and microcolony dispersion. These data provide a mechanism for how P. aeruginosa builds a matrix and subsequently a cavity to free a portion of cells for seeding dispersal. Direct visualization reveals that Psl is a key scaffolding matrix component and opens up avenues for therapeutics of biofilm-related complications

Domestication of Campylobacter jejuni NCTC 11168

Reference and type strains of well-known bacteria have been a cornerstone of microbiology research for decades. The sharing of well-characterized isolates among laboratories has run in parallel with research efforts and enhanced the reproducibility of experiments, leading to a wealth of knowledge about trait variation in different species and the underlying genetics. Campylobacter jejuni strain NCTC 11168, deposited at the National Collection of Type Cultures in 1977, has been adopted widely as a reference strain by researchers worldwide and was the first Campylobacter for which the complete genome was published (in 2000). In this study, we collected 23 C . jejuni NCTC 11168 reference isolates from laboratories across the UK and compared variation in simple laboratory phenotypes with genetic variation in sequenced genomes. Putatively identical isolates, identified previously to have aberrant phenotypes, varied by up to 281 SNPs (in 15 genes) compared to the most recent reference strain. Isolates also display considerable phenotype variation in motility, morphology, growth at 37 °C, invasion of chicken and human cell lines, and susceptibility to ampicillin. This study provides evidence of ongoing evolutionary change among C. jejuni isolates as they are cultured in different laboratories and highlights the need for careful consideration of genetic variation within laboratory reference strains. This article contains data hosted by Microreact