Covalent polyester colouration by in situ chromophore creation

The permanent colouration of a polyester by straightforward azo coupling is disclosed. Uniquely, the chromophore is created only upon successful polymer modification with a non-coloured molecule (in situ colouration), which confirms successful polymer adaptation and ensures that coloured waste is not produced. The method of colouration, which may feasibly be applied for the coloration of a wide-range of step-growth polyesters, yielded a polymer capable of preventing indigo deposition onto a range of fabrics, offering potential use within advanced detergent formulations

Correction: Thermoresponsive polysarcosine-based nanoparticles

Correction for ‘Thermoresponsive polysarcosine-based nanoparticles’ by Huayang Yu et al., J. Mater. Chem. B, 2019, 7, 4217–4223

Meticulous Doxorubicin Release from pH‐responsive Nanoparticles Entrapped within an Injectable Thermoresponsive Depot.

The dual stimuli‐controlled release of doxorubicin from gel‐embedded nanoparticles is reported. Non‐cytotoxic polymer nanoparticles are formed from poly(ethylene glycol)‐ b ‐poly(benzyl glutamate) that, uniquely, contain a central ester link. This connection renders the nanoparticles pH‐responsive, enabling extensive doxorubicin release in acidic solutions (pH 6.5), but not in solutions of physiological pH (pH 7.4). Doxorubicin loaded nanoparticles were found to be stable for at least 31 days and lethal against the three breast cancer cell lines tested. Furthermore, doxorubicin loaded nanoparticles could be incorporated within a thermoresponsive poly(2‐hydroxypropyl methacrylate) gel depot, which forms immediately upon injection of poly(2‐hydroxypropyl methacrylate) in DMSO solution into aqueous solution. The combination of the poly(2‐hydroxypropyl methacrylate) gel and poly(ethylene glycol)‐ b ‐poly(benzyl glutamate) nanoparticles yields an injectable doxorubicin delivery system that facilities near‐complete drug release when maintained at elevated temperatures (37 °C) in acidic solution (pH 6.5). In contrast, negligible payload release occurs when the material is stored at room temperature in non‐acidic solution (pH 7.4). The system has great potential as a vehicle for the prolonged, site‐specific, release of chemotherapeutics

Poly(amino acid)-polyester graft copolymer nanoparticles for the acid-mediated release of doxorubicin

Biodegradable polymers have emerged as highly effective drug delivery vehicles. We combine N-carboxyanhydride and O-carboxyanhydride ring opening polymerisations to synthesise a poly(amino acid)-polyester graft copolymer capable of encapsulating, and subsequently releasing doxorubicin via acid-mediated hydrolysis. Consequently, the nanoparticles detailed are extremely promising vehicles for the controlled delivery of chemotherapeutic agents

3D Visualisation of Additive Occlusion and Tunable Full-Spectrum Fluorescence in Calcite

From biomineralization to synthesis, organic additives provide an effective means of controlling crystallisation processes. There is growing evidence that these additives are often occluded within the crystal lattice, where this promises an elegant means of creating nanocomposites and tuning physical properties. Here, we use the incorporation of sulfonated fluorescent dyes to gain new understanding of additive occlusion in calcite (CaCO3), and to link morphological changes to occlusion mechanisms. We demonstrate that these additives are incorporated within specific zones, as defined by the growth conditions, and show how occlusion can govern changes in crystal shape. Fluorescence spectroscopy and lifetime imaging microscopy also show that the dyes experience unique local environments within different zones. Our strategy was then extended to simultaneously incorporate mixtures of dyes, whose fluorescence cascade creates calcite nanoparticles that fluoresce white. This offers a simple strategy for generating biocompatible and stable fluorescent nanoparticles whose output can be tuned as required

Interleukin-1β sequesters hypoxia inducible factor 2α to the primary cilium.

BACKGROUND: The primary cilium coordinates signalling in development, health and disease. Previously we have shown that the cilium is essential for the anabolic response to loading and the inflammatory response to interleukin-1β (IL-1β). We have also shown the primary cilium elongates in response to IL-1β exposure. Both anabolic phenotype and inflammatory pathology are proposed to be dependent on hypoxia-inducible factor 2 alpha (HIF-2α). The present study tests the hypothesis that an association exists between the primary cilium and HIFs in inflammatory signalling. RESULTS: Here we show, in articular chondrocytes, that IL-1β-induces primary cilia elongation with alterations to cilia trafficking of arl13b. This elongation is associated with a transient increase in HIF-2α expression and accumulation in the primary cilium. Prolyl hydroxylase inhibition results in primary cilia elongation also associated with accumulation of HIF-2α in the ciliary base and axoneme. This recruitment and the associated cilia elongation is not inhibited by blockade of HIFα transcription activity or rescue of basal HIF-2α expression. Hypomorphic mutation to intraflagellar transport protein IFT88 results in limited ciliogenesis. This is associated with increased HIF-2α expression and inhibited response to prolyl hydroxylase inhibition. CONCLUSIONS: These findings suggest that ciliary sequestration of HIF-2α provides negative regulation of HIF-2α expression and potentially activity. This study indicates, for the first time, that the primary cilium regulates HIF signalling during inflammation

Balancing Selection at the Tomato RCR3 Guardee Gene Family Maintains Variation in Strength of Pathogen Defense

Coevolution between hosts and pathogens is thought to occur between interacting molecules of both species. This results in the maintenance of genetic diversity at pathogen antigens (or so-called effectors) and host resistance genes such as the major histocompatibility complex (MHC) in mammals or resistance (R) genes in plants. In plant-pathogen interactions, the current paradigm posits that a specific defense response is activated upon recognition of pathogen effectors via interaction with their corresponding R proteins. According to the''Guard-Hypothesis,'' R proteins (the ``guards'') can sense modification of target molecules in the host (the ``guardees'') by pathogen effectors and subsequently trigger the defense response. Multiple studies have reported high genetic diversity at R genes maintained by balancing selection. In contrast, little is known about the evolutionary mechanisms shaping the guardee, which may be subject to contrasting evolutionary forces. Here we show that the evolution of the guardee RCR3 is characterized by gene duplication, frequent gene conversion, and balancing selection in the wild tomato species Solanum peruvianum. Investigating the functional characteristics of 54 natural variants through in vitro and in planta assays, we detected differences in recognition of the pathogen effector through interaction with the guardee, as well as substantial variation in the strength of the defense response. This variation is maintained by balancing selection at each copy of the RCR3 gene. Our analyses pinpoint three amino acid polymorphisms with key functional consequences for the coevolution between the guardee (RCR3) and its guard (Cf-2). We conclude that, in addition to coevolution at the ``guardee-effector'' interface for pathogen recognition, natural selection acts on the ``guard-guardee'' interface. Guardee evolution may be governed by a counterbalance between improved activation in the presence and prevention of auto-immune responses in the absence of the corresponding pathogen

Camels and Climate Resilience: Adaptation in Northern Kenya

In the drylands of Africa, pastoralists have been facing new challenges, including those related to environmental shocks and stresses. In northern Kenya, under conditions of reduced rainfall and more frequent droughts, one response has been for pastoralists to focus increasingly on camel herding. Camels have started to be kept at higher altitudes and by people who rarely kept camels before. The development has been understood as a climate change adaptation strategy and as a means to improve climate resilience. Since 2003, development organizations have started to further the trend by distributing camels in the region. Up to now, little has been known about the nature of, reasons for, or ramifications of the increased reliance on camels. The paper addresses these questions and concludes that camels improve resilience in this dryland region, but only under certain climate change scenarios, and only for some groups.This study was funded by The Royal Geographical Society with Institute of British Geographers Thesiger-Oman Fellowship

Potentially toxic metals in historic landfill sites: Implications for grazing animals

Municipal waste disposal is an increasing global problem, frequently solved by the use of landfill sites. Following closure, such sites contain a legacy of pollutants and must be managed to provide a safe and useful end life. The soils and vegetation from four historic landfill sites were analysed to determine the extent of pollution by potentially toxic metals (PTMs). Data were subsequently assessed to determine if post closure uses involving grazing were safe for the animals. The heaviest and widest spread soil contamination was due to Ni. Concentrations at all sites exceeded the 95th percentile value for rural soils, in one case by a factor of 30. Cu and Pb contamination was identified at some sites, but no evidence of Al or Zn contamination was found. Oral bioaccessibility testing showed that the availability of Ni in soil was exceedingly low, whilst that of Cu and Pb was high. Concentrations in plant shoots differed significantly amongst the sites, but interspecific differences in shoot concentration were only significant in the case of Cu. The results indicated that exposure levels to grazers would be at or below tolerable levels, indicating that it is generally safe to graze historic landfill. However, animals could be exposed to higher levels of PTMs than would be expected from rural locations, and grazing under conditions where soil consumption may be high could result in levels of exposure to Al, Ni and Pb exceeding tolerable levels. © Springer International Publishing 2014

Evaluation of expressive writing for postpartum health: A randomized controlled trial

Pregnancy, birth and adjusting to a new baby is a potentially stressful time that can negatively affect the health of women. There is some evidence that expressive writing can have positive effects on psychological and physical health, particularly during stressful periods. The current study aimed to evaluate whether expressive writing would improve women’s postpartum health. A randomized controlled trial was conducted with three conditions: expressive writing (n=188), a control writing task (n=213), or normal care (n=163). Measures of psychological health, physical health and quality of life were measured at baseline (6-12 weeks postpartum), 1 month and 6 months later. Ratings of stress were taken before and after the expressive writing task. Intent-to-treat analyses showed no significant differences between women in the expressive writing, control writing and normal care groups on measures of physical health, anxiety, depression, mood or quality of life at 1 and 6 months. Uptake and adherence to the writing tasks was low. However, women in the expressive writing group rated their stress as significantly reduced after completing the task. Cost analysis suggest women who did expressive writing had the lowest costs in terms of healthcare service use and lowest cost per unit of improvement in quality of life. Results suggest expressive writing is not effective as a universal intervention for all women 6-12 weeks postpartum. Future research should examine expressive writing as a targeted intervention for women in high-risk groups, such as those with mild or moderate depression, and further examine cost-effectiveness