Cyclic di-GMP is Essential for the Survival of the Lyme Disease Spirochete in Ticks

Cyclic dimeric GMP (c-di-GMP) is a bacterial second messenger that modulates many biological processes. Although its role in bacterial pathogenesis during mammalian infection has been documented, the role of c-di-GMP in a pathogen's life cycle within a vector host is less understood. The enzootic cycle of the Lyme disease pathogen Borrelia burgdorferi involves both a mammalian host and an Ixodes tick vector. The B. burgdorferi genome encodes a single copy of the diguanylate cyclase gene (rrp1), which is responsible for c-di-GMP synthesis. To determine the role of c-di-GMP in the life cycle of B. burgdorferi, an Rrp1-deficient B. burgdorferi strain was generated. The rrp1 mutant remains infectious in the mammalian host but cannot survive in the tick vector. Microarray analyses revealed that expression of a four-gene operon involved in glycerol transport and metabolism, bb0240-bb0243, was significantly downregulated by abrogation of Rrp1. In vitro, the rrp1 mutant is impaired in growth in the media containing glycerol as the carbon source (BSK-glycerol). To determine the contribution of the glycerol metabolic pathway to the rrp1 mutant phenotype, a glp mutant, in which the entire bb0240-bb0243 operon is not expressed, was generated. Similar to the rrp1 mutant, the glp mutant has a growth defect in BSK-glycerol medium. In vivo, the glp mutant is also infectious in mice but has reduced survival in ticks. Constitutive expression of the bb0240-bb0243 operon in the rrp1 mutant fully rescues the growth defect in BSK-glycerol medium and partially restores survival of the rrp1 mutant in ticks. Thus, c-di-GMP appears to govern a catabolic switch in B. burgdorferi and plays a vital role in the tick part of the spirochetal enzootic cycle. This work provides the first evidence that c-di-GMP is essential for a pathogen's survival in its vector host

Production of human metabolites of the anti-cancer drug flutamide via biotransformation in Cunninghamella species

Fungi belonging to the genus Cunninghamella have enzymes similar to those employed by mammals for the detoxification of xenobiotics, thus they are useful as models of mammalian drug metabolism, and as a source for drug metabolites. We report the transformation of the anti-cancer drug flutamide in Cunninghamella sp. The most predominant phase I metabolites present in the plasma of humans, 2-hydroxyflutamide and 4-nitro-3-(trifluoromethyl)aniline, were also produced in Cunninghamella cultures. Other phase I and phase II metabolites were also detected using a combination of HPLC, GC–MS and 19F-NMR.SB. 30/4/201

Mindfulness in the academy : An examination of mindfulness perspectives

In a complex and demanding higher education, environment wellness for scholars is an ethical imperative and is an essential component of self-care, required to prevent burnout, distress, and impairment. As we navigate the contemporary higher education environment, it is important to look at ways of working that bring to the forefront self-care and mindfulness. In this chapter, we explore how scholars understand and apply the concept of mindfulness in higher education contexts. We examine ways academics implement mindfulness practices that build the capacity to accept, tolerate and transform mind and body states without reacting so intensively to them by drawing on concepts such as compassion, kindness, gratitude, curiosity, self-awareness and non-judgmental stances. We explore how mindful ways of researching, writing, learning and teaching, leading and engaging with others leads us to be self-aware and engaged in the present. We introduce the notion of Dramaturgical Theory of Social Interaction as a framework for examining mindful practices in academia. This chapter presents a thematic analysis of the work of the authors presented in this volume, situating this in a broader discussion of mindfulness, and we raise questions for further consideration

36Cl bomb pulse measured in a shallow ice core from Dye 3, Greenland

Nuclear weapons tests at oceanic sites during the 1950s produced a large amount of 36Cl (t1/2 = 3.0 × 105 yr) through neutron capture of 35Cl in seawater. Part of this anthropogenic 36Cl was injected into the stratosphere from where it was redistributed throughout the Earth. This pulse of 36Cl was first detected in rainfall by Schaeffer et al.(1). The global deposition rates are several orders of magnitude larger than the natural pre-and post-bomb 36Cl production rate that reflects cosmic-ray spallation of atmospheric 40Ar. Because 36Cl is not a fission product, the anthropogenic 36Cl is produced mainly in marine tests carried out on small islands and barges where a large amount of seawater chlorine is present to serve as a target. This target element requirement leads to a temporal dependence different from the other bomb produced isotopes(2–4). We have determined the temporal dependence of 36Cl fallout by measuring the depth profile of 36Cl in an ice core from Dye 3 Greenland (65° 11′ N, 43° 50′ W) using tandem accelerator mass spectrometry(5). We show here that the results agree well with a calculation of the 36Cl produced and injected into the stratosphere by the tests