The Influence of the Toxin/Antitoxin mazEF on Growth and Survival of Listeria monocytogenes under Stress

A major factor in the resilience of Listeria monocytogenes is the alternative sigma factor B (σB). Type II Toxin/Antitoxin (TA) systems are also known to have a role in the bacterial stress response upon activation via the ClpP or Lon proteases. Directly upstream of the σB operon in L. monocytogenes is the TA system mazEF, which can cleave mRNA at UACMU sites. In this study, we showed that the mazEF TA locus does not affect the level of persister formation during treatment with antibiotics in lethal doses, but exerts different effects according to the sub-inhibitory stress added. Growth of a ΔmazEF mutant was enhanced relative to the wildtype in the presence of sub-inhibitory norfloxacin and at 42 °C, but was decreased when challenged with ampicillin and gentamicin. In contrast to studies in Staphylococcus aureus, we found that the mazEF locus did not affect transcription of genes within the σB operon, but MazEF effected the expression of the σB-dependent genes opuCA and lmo0880, with a 0.22 and 0.05 fold change, respectively, compared to the wildtype under sub-inhibitory norfloxacin conditions. How exactly this system operates remains an open question, however, our data indicates it is not analogous to the system of S. aureus, suggesting a novel mode of action for MazEF in L. monocytogenes

Graphic loans: East Asia and beyond

The national languages of East Asia (Chinese, Japanese, Korean and Vietnamese) have made extensive use of a type of linguistic borrowing sometimes referred to as a 'graphic loan'. Such loans have no place in the conventional classification of loans based on Haugen (1950) or Weinreich (1953), and research on loan word theory and phonology generally overlooks them. The classic East Asian phenomenon is discussed and a framework is proposed to describe its mechanism. It is argued that graphic loans are more than just 'spelling pronunciations', because they are a systematic and widespread process, independent of but not inferior to phonological borrowing. The framework is then expanded to cover a range of other cases of borrowing between languages to show that graphic loans are not a uniquely East Asian phenomenon, and therefore need to be considered as a major category of loan

Formulation, stabilisation and encapsulation of bacteriophage for phage therapy

Against a backdrop of global antibiotic resistance and increasing awareness of the importance of the human microbiota, there has been resurgent interest in the potential use of bacteriophages for therapeutic purposes, known as phage therapy. A number of phage therapy phase I and II clinical trials have concluded, and shown phages don’t present significant adverse safety concerns. These clinical trials used simple phage suspensions without any formulation and phage stability was of secondary concern. Phages have a limited stability in solution, and undergo a significant drop in phage titre during processing and storage which is unacceptable if phages are to become regulated pharmaceuticals, where stable dosage and well defined pharmacokinetics and pharmacodynamics are de rigueur. Animal studies have shown that the efficacy of phage therapy outcomes depend on the phage concentration (i.e. the dose) delivered at the site of infection, and their ability to target and kill bacteria, arresting bacterial growth and clearing the infection. In addition, in vitro and animal studies have shown the importance of using phage cocktails rather than single phage preparations to achieve better therapy outcomes. The in vivo reduction of phage concentration due to interactions with host antibodies or other clearance mechanisms may necessitate repeated dosing of phages, or sustained release approaches. Modelling of phage-bacterium population dynamics reinforces these points. Surprisingly little attention has been devoted to the effect of formulation on phage therapy outcomes, given the need for phage cocktails, where each phage within a cocktail may require significantly different formulation to retain a high enough infective dose. This review firstly looks at the clinical needs and challenges (informed through a review of key animal studies evaluating phage therapy) associated with treatment of acute and chronic infections and the drivers for phage encapsulation. An important driver for formulation and encapsulation is shelf life and storage of phage to ensure reproducible dosages. Other drivers include formulation of phage for encapsulation in micro- and nanoparticles for effective delivery, encapsulation in stimuli responsive systems for triggered controlled or sustained release at the targeted site of infection. Encapsulation of phage (e.g. in liposomes) may also be used to increase the circulation time of phage for treating systemic infections, for prophylactic treatment or to treat intracellular infections. We then proceed to document approaches used in the published literature on the formulation and stabilisation of phage for storage and encapsulation of bacteriophage in micro- and nanostructured materials using freeze drying (lyophilization), spray drying, in emulsions e.g. ointments, polymeric microparticles, nanoparticles and liposomes. As phage therapy moves forward towards Phase III clinical trials, the review concludes by looking at promising new approaches for micro- and nanoencapsulation of phages and how these may address gaps in the field

Hermeneutics of Acrostics: From Kūkai to Tsurayuki

This study is an attempt to show how the poetic figure of the acrostic was constructed in ninth-century Japan as a tantric semiological implement in a poetic discourse, in which poets working in Sino-Japanese or kanabun constructed kami cultic ritual in various forms and contexts within the broad framework of Kūkai’s tantric Buddhist semiology. Three poetic texts, a Sino-Japanese poem by Kūkai and two prose-poem texts from Kokin wakashū and/or Ise monogatari, all of which contain an acrostic, are analysed and interpreted, and evidence from several of Kūkai’s expositions on semiology (philosophy of language) and hermeneutics, is adduced in support. The suggestion is that the acrostic was construed as an articulation of Kūkai’s metaphor for the limitlessness of meanings of the mantra syllables, the intersection of vertical and horizontal meanings, which was associated with the experience of nyūga ganyū 入我我入 (Skt. ahaṃkāra)