Gene-Trap Mutagenesis Identifies Mammalian Genes Contributing to Intoxication by Clostridium perfringens ε-Toxin

The Clostridium perfringens ε-toxin is an extremely potent toxin associated with lethal toxemias in domesticated ruminants and may be toxic to humans. Intoxication results in fluid accumulation in various tissues, most notably in the brain and kidneys. Previous studies suggest that the toxin is a pore-forming toxin, leading to dysregulated ion homeostasis and ultimately cell death. However, mammalian host factors that likely contribute to ε-toxin-induced cytotoxicity are poorly understood. A library of insertional mutant Madin Darby canine kidney (MDCK) cells, which are highly susceptible to the lethal affects of ε-toxin, was used to select clones of cells resistant to ε-toxin-induced cytotoxicity. The genes mutated in 9 surviving resistant cell clones were identified. We focused additional experiments on one of the identified genes as a means of validating the experimental approach. Gene expression microarray analysis revealed that one of the identified genes, hepatitis A virus cellular receptor 1 (HAVCR1, KIM-1, TIM1), is more abundantly expressed in human kidney cell lines than it is expressed in human cells known to be resistant to ε-toxin. One human kidney cell line, ACHN, was found to be sensitive to the toxin and expresses a larger isoform of the HAVCR1 protein than the HAVCR1 protein expressed by other, toxin-resistant human kidney cell lines. RNA interference studies in MDCK and in ACHN cells confirmed that HAVCR1 contributes to ε-toxin-induced cytotoxicity. Additionally, ε-toxin was shown to bind to HAVCR1 in vitro. The results of this study indicate that HAVCR1 and the other genes identified through the use of gene-trap mutagenesis and RNA interference strategies represent important targets for investigation of the process by which ε-toxin induces cell death and new targets for potential therapeutic intervention

Mutual Distrust: Perspectives From Researchers and Policy Makers on the Research to Policy Gap in 2013 and Recommendations for the Future

The production of health policy-relevant research is necessary, but not sufficient, to promote its utilization in policy. Our objective was to understand the perspectives of United States’ state-level policy makers and health researchers on the barriers and facilitators to the translation of health evidence into the policy process, with a particular focus on issues related to relationship building. We conducted interviews with 215 US health services and health policy researchers and 40 state-level staffers and legislators. Researchers and policy makers faced the same major barrier to research translation: lack of dedicated time to do so. Some policy makers questioned the credibility of research, and researchers questioned policy makers’ authentic desire to use evidence in decision making. For some study participants, a mutual mistrust of the other group challenges stronger relationship formation. Interventions are needed to help both groups understand a broader role that research plays in policy making and to increase personal contact, and ultimately trusted relationships, across various actors in the policy process

Resetting the table for people and plants: Botanic gardens and research organizations collaborate to address food and agricultural plant blindness

Societal Impact Statement Food and agricultural plants are integral to human well‐being. Due to their universal importance, such plants would appear to represent an ideal entryway by which to address plant blindness. However, with limited opportunities for direct contact with agriculture, many people cannot appreciate the flora that feed us every day. We provide examples of informal education initiatives aimed at increasing public awareness and appreciation of food and agricultural plants, made possible through collaborations between botanic gardens, academic institutions, nonprofits, and agricultural research organizations. We hope these examples encourage and inspire organizations to further utilize food and agricultural plants to tackle plant blindness. Summary Of the myriad gifts plants provide to humanity, food is among the most visible, as everyone needs to eat, every single day. Due to their universal importance, food and agricultural plants would appear to represent ideal entryways to address plant blindness. Yet increasing urbanization worldwide and decreasing proportions of the global workforce in agriculture are limiting opportunities for people to have direct, hands‐on experiences with food and agricultural plants outside of retail purchasing, meal preparation, and food consumption. This disconnect is troubling, especially as the challenges to the sustainability of our future food supply necessitate that society, and certainly elected decision‐makers, have the capacity to understand the potential benefits, risks, and tradeoffs inherent to agriculture and its advancing technologies. We outline opportunities to address agricultural plant blindness with emphasis on current complex issues within the food and agriculture sector. We provide examples of fruitful collaborations between botanic gardens, academic institutions, nonprofits, and agricultural research organizations that engage people around these issues

Mutual Distrust: Perspectives From Researchers and Policy Makers on the Research to Policy Gap in 2013 and Recommendations for the Future

The production of health policy-relevant research is necessary, but not sufficient, to promote its utilization in policy. Our objective was to understand the perspectives of United States’ state-level policy makers and health researchers on the barriers and facilitators to the translation of health evidence into the policy process, with a particular focus on issues related to relationship building. We conducted interviews with 215 US health services and health policy researchers and 40 state-level staffers and legislators. Researchers and policy makers faced the same major barrier to research translation: lack of dedicated time to do so. Some policy makers questioned the credibility of research, and researchers questioned policy makers’ authentic desire to use evidence in decision making. For some study participants, a mutual mistrust of the other group challenges stronger relationship formation. Interventions are needed to help both groups understand a broader role that research plays in policy making and to increase personal contact, and ultimately trusted relationships, across various actors in the policy process