Conserved Mutations in the Pneumococcal Bacteriocin Transporter Gene, blpA, Result in a Complex Population Consisting of Producers and Cheaters

All fully sequenced strains of Streptococcus pneumoniae possess a version of the blp locus, which is responsible for bacteriocin production and immunity. Activation of the blp locus is stimulated by accumulation of the peptide pheromone, BlpC, following its secretion by the ABC transporter, BlpA. The blp locus is characterized by significant diversity in blpC type and in the region of the locus containing putative bacteriocin and immunity genes. In addition, the blpA gene can represent a single large open reading frame or be divided into several smaller fragments due to the presence of frameshift mutations. In this study, we use a collection of strains with blp-dependent inhibition and immunity to define the genetic changes that bring about phenotypic differences in bacteriocin production or immunity. We demonstrate that alterations in blpA, blpC, and bacteriocin/immunity content likely play an important role in competitive interactions between pneumococcal strains. Importantly, strains with a highly conserved frameshift mutation in blpA are unable to secrete bacteriocins or BlpC, but retain the ability to respond to exogenous peptide pheromone produced by cocolonizing strains, stimulating blp-mediated immunity. These “cheater” strains can only coexist with bacteriocin-producing strains that secrete their cognate BlpC and share the same immunity proteins. The variable outcome of these interactions helps to explain the heterogeneity of the blp pheromone, bacteriocin, and immunity protein content

Conditional deletion of hypothalamic Y2 receptors reverts gonadectomy-induced bone loss in adult mice

Reduction in levels of sex hormones at menopause in women is associated with two common, major outcomes, the accumulation of white adipose tissue, and the progressive loss of bone because of excess osteoclastic bone resorption exceeding osteoblastic bone formation. Current antiresorptive therapies can reduce osteoclastic activity but have only limited capacity to stimulate osteoblastic bone formation and restore lost skeletal mass. Likewise, the availability of effective pharmacological weight loss treatments is currently limited. Here we demonstrate that conditional deletion of hypothalamic neuropeptide Y2 receptors can prevent ongoing bone loss in sex hormone-deficient adult male and female mice. This benefit is attributable solely to activation of an anabolic osteoblastic bone formation response that counterbalances persistent elevation of bone resorption, suggesting the Y2-mediated anabolic pathway to be independent of sex hormones. Furthermore, the increase in fat mass that typically occurs after ovariectomy is prevented by germ line deletion of Y2 receptors, whereas in male mice body weight and fat mass were consistently lower than wild-type regardless of sex hormone status. Therefore, this study indicates a role for Y2 receptors in the accumulation of adipose tissue in the hypogonadal state and demonstrates that hypothalamic Y2 receptors constitutively restrain osteoblastic activity even in the absence of sex hormones. The increase in bone formation after release of this tonic inhibition suggests a promising new avenue for osteoporosis treatment

Sensory and Quasi-Sensory Experiences of the Deceased in Bereavement : An Interdisciplinary and Integrative Review

Bereaved people often report having sensory and quasi-sensory experiences of the deceased (SED), and there is an ongoing debate over whether SED are associated with pathology, such as grief complications. Research into these experiences has been conducted in various disciplines, including psychiatry, psychology, and anthropology, without much crossover. This review brings these areas of research together, drawing on the expertise of an interdisciplinary working group formed as part of the International Consortium for Hallucination Research (ICHR). It examines existing evidence on the phenomenology, associated factors, and impact of SED, including the role of culture, and discusses the main theories on SED and how these phenomena compare with unusual experiences in other contexts. The review concludes that the vast majority of these experiences are benign and that they should be considered in light of their biographical, relational, and sociocultural contexts

Each time I'm reminded of it, I feel as though I need therapy. Australian Football, Tragedies and the Question of Catharsis

Australian Football League fans often narrate particularly distressing final losses in tragic terms. Drawing from the field of tragedy studies, this paper examines the way such losses are experienced and told, and the suffering and possible pleasures these accounts reveal. How, I ask, do these losses engender so much pain? And why do fans continually return to their memories of these defeats, when each return reawakens the grief? These questions lead me to consider the relationship of tragedy to trauma, and the contentious nature and meaning of catharsis, a term common to the analysis of both tragedy and sport