Type III Secretion Is Essential for the Rapidly Fatal Diarrheal Disease Caused by Non-O1, Non-O139 Vibrio cholerae

Cholera is a severe diarrheal disease typically caused by O1 serogroup strains of Vibrio cholerae. The pathogenicity of all pandemic V. cholerae O1 strains relies on two critical virulence factors: cholera toxin, a potent enterotoxin, and toxin coregulated pilus (TCP), an intestinal colonization factor. However, certain non-O1, non-O139 V. cholerae strains, such as AM-19226, do not produce cholera toxin or TCP, yet they still cause severe diarrhea. The molecular basis for the pathogenicity of non-O1, non-O139 V. cholerae has not been extensively characterized, but many of these strains encode related type III secretion systems (TTSSs). Here, we used infant rabbits to assess the contribution of the TTSS to non-O1, non-O139 V. cholerae pathogenicity. We found that all animals infected with wild-type AM-19226 developed severe diarrhea even more rapidly than rabbits infected with V. cholerae O1. Unlike V. cholerae O1 strains, which do not damage the intestinal epithelium in rabbits or humans, AM-19226 caused marked disruptions of the epithelial surface in the rabbit small intestine. TTSS proved to be essential for AM-19226 virulence in infant rabbits; an AM-19226 derivative deficient for TTSS did not elicit diarrhea, colonize the intestine, or induce pathological changes in the intestine. Deletion of either one of the two previously identified or two newly identified AM-19226 TTSS effectors reduced but did not eliminate AM-19226 pathogenicity, suggesting that at least four effectors contribute to this strain’s virulence. In aggregate, our results suggest that the TTSS-dependent virulence in non-O1, non-O139 V. cholerae represents a new type of diarrheagenic mechanism

Are wildcard events on infrastructure systems opportunities for transformational change?

Infrastructure systems face a number of pressing challenges relating to demographics, environment, finance and governance pressures. Furthermore, infrastructure mediates the way in which everyday lives are conducted; their form and function creating a persistence of unsustainable practice and behaviour that cannot be changed even if change is desired. There is a need to find means by which this obduracy can be broken so that new, more sustainable futures can be planned. This paper develops a methodology, taking concepts from both engineering and social science. Wild cards, or physical disruptions, are used to ‘destructively test’ complex infrastructure systems and the multi-level perspective is used as a framework for analysing the resulting data. This methodology was used to examine a number of case studies, and with focus groups consisting of a range of different infrastructure providers and managers, to gain a better understanding of systems’ sociotechnical characteristics and behaviours. A number of impactful ‘intervention points’ emerged that offered the opportunity to promote radical changes towards configurations of infrastructure systems that provide for ‘less’ physical infrastructure. This paper also examines the utility of wild cards as enablers of transition to these ‘less’ configurations and demonstrates how a ‘wild card scenario’ can be used to co-design infrastructure adaptation from with both infrastructure providers and users

Perspective on the Use of LNT for Radiation Protection and Risk Assessment By The U.S. Environmental Protection Agency

The U.S. Environmental Protection Agency (EPA) bases its risk assessments, regulatory limits, and nonregulatory guidelines for population exposures to low level ionizing radiation on the linear no-threshold (LNT) hypothesis, which assumes that the risk of cancer due to a low dose exposure is proportional to dose, with no threshold. The use of LNT for radiation protection purposes has been repeatedly endorsed by authoritative scientific advisory bodies, including the National Academy of Sciences’ BEIR Committees, whose recommendations form a primary basis of EPA’s risk assessment methodology. Although recent radiobiological findings indicate novel damage and repair processes at low doses, LNT is supported by data from both epidemiology and radiobiology. Given the current state of the science, the consensus positions of key scientific and governmental bodies, as well as the conservatism and calculational convenience of the LNT assumption, it is unlikely that EPA will modify this approach in the near future