Analyzing the cost-effectiveness of Lyme disease risk reduction approaches.

Lyme disease (LD) is endemic in many regions of the Northeastern United States. Given the elusive nature of the disease, a systematic approach to identify efficient interventions would be useful for policymakers in addressing LD. We used Markov modeling to investigate the efficiency of interventions. These interventions range from awareness-based to behavioral-based strategies. Targeting animal reservoirs of LD using fungal spray or bait boxes did not prove to be an effective intervention. Results of awareness-based interventions, including distribution of signage, fliers, and presentations, implementable in different geographical scales, suggest that policymakers should focus on these interventions, as they are both cost-effective and have the highest impact on lowering LD risk. Populations may lose focus of LD warnings over time, thus quick succession of these interventions is vital. Our modeling results identify the awareness-based intervention as the most cost-effective strategy to lower the number of LD cases. These results can aid in the establishment of effective LD risk reduction policy at various scales of implementation.

Adapter Proteins for Opposing Motors Interact Simultaneously with Nuclear Pore Protein Nup358.

Nup358 is a protein subunit of the nuclear pore complex that recruits the opposing microtubule motors kinesin-1 and dynein [via the dynein adaptor Bicaudal D2 (BicD2)] to the nuclear envelope. This pathway is important for positioning of the nucleus during the early steps of mitotic spindle assembly and also essential for an important process in brain development. It is unknown whether dynein and kinesin-1 interact with Nup358 simultaneously or whether they compete. Here, we have reconstituted and characterized a minimal complex of kinesin-1 light chain 2 (KLC2) and Nup358. The proteins interact through a W-acidic motif in Nup358, which is highly conserved among vertebrates but absent in insects. While Nup358 and KLC2 form predominantly monomers, their interaction results in the formation of 2:2 complexes, and the W-acidic motif is required for the oligomerization. In active motor complexes, BicD2 and KLC2 each form dimers. Notably, we show that the dynein adaptor BicD2 and KLC2 interact simultaneously with Nup358, resulting in the formation of 2:2:2 complexes. Mutation of the W-acidic motif results in the formation of 1:1:1 complexes. On the basis of our data, we propose that Nup358 recruits simultaneously one kinesin-1 motor and one dynein motor via BicD2 to the nucleus. We hypothesize that the binding sites are close enough to promote direct interactions between these motor recognition domains, which may be important for the regulation of the motility of these opposing motors. Our data provide important insights into a nuclear positioning pathway that is crucial for brain development and faithful chromosome segregation.

Risk Factors of Lyme Disease: An Intersection of Environmental Ecology and Systems Science.

Lyme disease (LD) cases have been on the rise throughout the United States, costing the healthcare system up to $1.3 billion per year, and making LD one of the greatest threats to public health. Factors influencing the number of LD cases range from environmental to system-level variables, but little is known about the influence of vegetation (canopy, understory, and ground cover) and human behavioral risk on LD cases and exposure to infected ticks. We determined the influence of various risk factors on the risk of exposure to infected ticks on 22 different walkways using multinomial logistic regression. The model classifies the walkways into high-risk and low-risk categories with 90% accuracy, in which the understory, human risk, and number of rodents are significant indicators. These factors should be managed to control the risk of transmission of LD to humans.