Recent advances in therapeutic delivery systems of bacteriophage and bacteriophage-encoded endolysins

Antibiotics have been the cornerstone of clinical management of bacterial infection since their discovery in the early 20th century. However, their widespread and often indiscriminate use has now led to reports of multidrug resistance becoming globally commonplace. Bacteriophage therapy has undergone a recent revival in battle against pathogenic bacteria, as the self-replicating and co-evolutionary features of these predatory virions offer several advantages over conventional therapeutic agents. In particular, the use of targeted bacteriophage therapy from specialized delivery platforms has shown particular promise owing to the control of delivery location, administration conditions and dosage of the therapeutic cargo. This review presents an overview of the recent formulations and applications of such delivery vehicles as an innovative and elegant tool for bacterial control. </jats:p

Prevention of encrustation and blockage of urinary catheters by:Proteus mirabilis via pH-triggered release of bacteriophage

The crystalline biofilms of Proteus mirabilis can seriously complicate the care of patients undergoing long-term indwelling urinary catheterisation. Expression of bacterial urease causes a significant increase in urinary pH, leading to the supersaturation and precipitation of struvite and apatite crystals. These crystals become lodged within the biofilm, resulting in the blockage of urine flow through the catheter. Here, we describe an infection-responsive surface coating for urinary catheters, which releases a therapeutic dose of bacteriophage in response to elevated urinary pH, in order to delay catheter blockage. The coating employs a dual-layered system comprising of a lower hydrogel 'reservoir' layer impregnated with bacteriophage, capped by a 'trigger' layer of the pH-responsive polymer poly(methyl methacrylate-co-methacrylic acid) (EUDRAGIT®S 100). Evaluation of prototype coatings using a clinically reflective in vitro bladder model system showed that catheter blockage time was doubled (13 h to 26 h (P < 0.05)) under conditions of established infection (108 CFU ml-1) in response to a 'burst-release' of bacteriophage (108 PFU ml-1). Coatings were stable both in the absence of infection, and in the presence of urease-negative bacteria. Quantitative and visual analysis of crystalline biofilm reduction show that bacteriophage constitute a promising strategy for the prevention of catheter blockage, a clinical problem for which there is currently no effective control method

Limiting Pseudomonas aeruginosa Biofilm Formation Using Cold Atmospheric Pressure Plasma

We investigate the ability to disrupt and limit growth biofilms of Pseudomonas aeruginosa using application of cold atmospheric pressure (CAP) plasma. The effect of the bio-film's exposure to a helium (CAP) jet was assessed at varying time points during biofilm maturation. Results showed that the amount of time during biofilm growth that CAP pressure was applied has a crucial role on the ability of biofilms to mature and recover after CAP exposure. Intervention during the early stages of biofilm formation (0-8 h) results in a 4-5-log reduction in viable bacterial cells (measured at 24 h of incubation) relative to untreated biofilms. However, CAP treatment of biofilm at 12 h and above only results in a 2-log reduction in viable cells. This has potentially important implications for future clinical application of CAP to treat infected wounds

Delivery and quantification of hydrogen peroxide generated via cold atmospheric pressure plasma through biological material

The ability of plasma-generated hydrogen peroxide (H 2O 2) to traverse bacterial biofilms and the subsequent fate of the generated H 2O 2 has been investigated. An in vitro model, comprising a nanoporous membrane impregnated with artificial wound fluid and biofilms of varying maturity was treated with a helium-driven, cold atmospheric pressure plasma (CAP) jet. The concentration of H 2O 2 generated below the biofilms was quantified. The results showed that the plasma-generated H 2O 2 interacted significantly with the biofilm, thus exhibiting a reduction in concentration across the underlying nanoporous membrane. Biofilm maturity exhibited a significant effect on the penetration depth of H 2O 2, suggesting that well established, multilayer biofilms are likely to offer a shielding effect with respect to cells located in the lower layers of the biofilm, thus rendering them less susceptible to plasma disinfection. This may prove clinically significant in the plasma treatment of chronic, deep tissue infections such as diabetic and venous leg ulcers. Our results are discussed in the context of plasma-biofilm interactions, with respect to the fate of the longer lived reactive species generated by CAP, such as H 2O

Development of an Infection-Responsive Fluorescent Sensor for the Early Detection of Urinary Catheter Blockage

Formation of crystalline biofilms following infection by <i>Proteus mirabilis</i> can lead to encrustation and blockage of long-term indwelling catheters, with serious clinical consequences. We describe a simple sensor, placed within the catheter drainage bag, to alert of impending blockage via a urinary color change. The pH-responsive sensor is a dual-layered polymeric “lozenge”, able to release the self-quenching dye 5(6)-carboxyfluorescein in response to the alkaline urine generated by the expression of bacterial urease. Sensor performance was evaluated within a laboratory model of the catheterized urinary tract, infected with both urease positive and negative bacterial strains under conditions of established infection, achieving an average “early warning” of catheter blockage of 14.5 h. Signaling only occurred following infection with urease positive bacteria. Translation of these sensors into a clinical environment would allow appropriate intervention before the occurrence of catheter blockage, a problem for which there is currently no effective control method

Ensemble Asteroseismology of Solar-Type Stars with the NASA Kepler Mission

In addition to its search for extra-solar planets, the NASA Kepler Mission provides exquisite data on stellar oscillations. We report the detections of oscillations in 500 solartype stars in the Kepler field of view, an ensemble that is large enough to allow statistical studies of intrinsic stellar properties (such as mass, radius and age) and to test theories of stellar evolution. We find that the distribution of observed masses of these stars shows intriguing differences to predictions from models of synthetic stellar populations in the Galaxy.Comment: 20 pages, including on-line supporting materia

Taking ELF off the shelf: Developing HE students' speaking skills through a focus on English as a lingua franca

This paper explores how principles derived from English as a lingua franca (ELF) research (e.g. accommodation, strategic competence) can provide insights into the speaking demands of group work in Anglophone EMI settings which includes native speakers as well as non-native speakers. The paper maps data gathered through interviews with first year undergraduate students against Mercer et al.’s (2017) oracy framework. It shows that students draw on a combination of linguistic, cognitive, physical and social & emotional skills, many of which align with ELF principles. However, current frameworks of support for speaking demands in HE (EAP and academic skills) lack focus on dialogic speaking, pay little heed to ELF findings and cater for native speakers and non-native speakers separately despite their needs being similar. The paper argues that a focus on ELF can contribute to the development of speaking support which sits at the centre of students’ academic journey and encourages better interactions between native and non-native speakers

Neural Circuits Underlying Rodent Sociality: A Comparative Approach

All mammals begin life in social groups, but for some species, social relationships persist and develop throughout the course of an individual’s life. Research in multiple rodent species provides evidence of relatively conserved circuitry underlying social behaviors and processes such as social recognition and memory, social reward, and social approach/avoidance. Species exhibiting different complex social behaviors and social systems (such as social monogamy or familiarity preferences) can be characterized in part by when and how they display specific social behaviors. Prairie and meadow voles are closely related species that exhibit similarly selective peer preferences but different mating systems, aiding direct comparison of the mechanisms underlying affiliative behavior. This chapter draws on research in voles as well as other rodents to explore the mechanisms involved in individual social behavior processes, as well as specific complex social patterns. Contrasts between vole species exemplify how the laboratory study of diverse species improves our understanding of the mechanisms underlying social behavior. We identify several additional rodent species whose interesting social structures and available ecological and behavioral field data make them good candidates for study. New techniques and integration across laboratory and field settings will provide exciting opportunities for future mechanistic work in non-model species

The Solar Orbiter Science Activity Plan: translating solar and heliospheric physics questions into action

Solar Orbiter is the first space mission observing the solar plasma both in situ and remotely, from a close distance, in and out of the ecliptic. The ultimate goal is to understand how the Sun produces and controls the heliosphere, filling the Solar System and driving the planetary environments. With six remote-sensing and four in-situ instrument suites, the coordination and planning of the operations are essential to address the following four top-level science questions: (1) What drives the solar wind and where does the coronal magnetic field originate?; (2) How do solar transients drive heliospheric variability?; (3) How do solar eruptions produce energetic particle radiation that fills the heliosphere?; (4) How does the solar dynamo work and drive connections between the Sun and the heliosphere? Maximising the mission’s science return requires considering the characteristics of each orbit, including the relative position of the spacecraft to Earth (affecting downlink rates), trajectory events (such as gravitational assist manoeuvres), and the phase of the solar activity cycle. Furthermore, since each orbit’s science telemetry will be downloaded over the course of the following orbit, science operations must be planned at mission level, rather than at the level of individual orbits. It is important to explore the way in which those science questions are translated into an actual plan of observations that fits into the mission, thus ensuring that no opportunities are missed. First, the overarching goals are broken down into specific, answerable questions along with the required observations and the so-called Science Activity Plan (SAP) is developed to achieve this. The SAP groups objectives that require similar observations into Solar Orbiter Observing Plans, resulting in a strategic, top-level view of the optimal opportunities for science observations during the mission lifetime. This allows for all four mission goals to be addressed. In this paper, we introduce Solar Orbiter’s SAP through a series of examples and the strategy being followed