Glycosaminoglycan Binding Facilitates Entry of a Bacterial Pathogen into Central Nervous Systems

Certain microbes invade brain microvascular endothelial cells (BMECs) to breach the blood-brain barrier (BBB) and establish central nervous system (CNS) infection. Here we use the leading meningitis pathogen group B Streptococcus (GBS) together with insect and mammalian infection models to probe a potential role of glycosaminoglycan (GAG) interactions in the pathogenesis of CNS entry. Site-directed mutagenesis of a GAG-binding domain of the surface GBS alpha C protein impeded GBS penetration of the Drosophila BBB in vivo and diminished GBS adherence to and invasion of human BMECs in vitro. Conversely, genetic impairment of GAG expression in flies or mice reduced GBS dissemination into the brain. These complementary approaches identify a role for bacterial-GAG interactions in the pathogenesis of CNS infection. Our results also highlight how the simpler yet genetically conserved Drosophila GAG pathways can provide a model organism to screen candidate molecules that can interrupt pathogen-GAG interactions for future therapeutic applications

The ontogeny of antipredator behavior: age differences in California ground squirrels (Otospermophilus beecheyi) at multiple stages of rattlesnake encounters

Newborn offspring of animals often exhibit fully functional innate antipredator behaviors, but they may also require learning or further development to acquire appropriate responses. Experience allows offspring to modify responses to specific threats and also leaves them vulnerable during the learning period. However, antipredator behaviors used at one stage of a predator encounter may compensate for deficiencies at another stage, a phenomenon that may reduce the overall risk of young that are vulnerable at one or more stages. Few studies have examined age differences in the effectiveness of antipredator behaviors across multiple stages of a predator encounter. In this study, we examined age differences in the antipredator behaviors of California ground squirrels (Otospermophilus beecheyi) during the detection, interaction, and attack stages of Pacific rattlesnake (Crotalus oreganus) encounters. Using free-ranging squirrels, we examined the ability to detect free-ranging rattlesnakes, snake-directed behaviors after discovery of a snake, and responses to simulated rattlesnake strikes. We found that age was the most important factor in snake detection, with adults being more likely to detect snakes than pups. We also found that adults performed more tail flagging (a predator-deterrent signal) toward snakes and were more likely to investigate a snake’s refuge when interacting with a hidden snake. In field experiments simulating snake strikes, adults exhibited faster reaction times than pups. Our results show that snake detection improves with age and that pups probably avoid rattlesnakes and minimize time spent in close proximity to them to compensate for their reduced reaction times to strikes

Financial stress and strain associated with terminal cancer:a review of the evidence

Financial circumstances are a significant influence on the quality of life for older people and may be important to health and wellbeing at the end of life. The aim of this study is to review the evidence for the existence and consequences of financial stress and strain at the end of life for people dying with cancer. We conducted a systematic search of four electronic databases for studies, providing data on illness-related financial burden (stress), or perception of financial hardship (strain), from patients with terminal cancer or their caregivers. Twenty-four papers were identified from 21 studies published in English between 1980 and 2006, the majority (14) of cross-sectional design. Financial stress was reported in all 13 studies from the USA (median 33%, range 10-66%), but only four sought measures of financial strain. In the USA, specific social consequences, such as moving house or change in employment to cope with caregiving, were reported in four of these studies; one of these also noted changes in treatment choices and avoidance of care for other family members. In studies from outside the USA, there is a dearth of data on financial stresses and the consequences of this for the household, despite widespread reporting of financial strain. To fill a gap in our understanding and improve holistic palliative care, researchers need to ask the questions about the consequences of financial stresses and strain for the health and wellbeing of the household