Plasmodium knowlesi: a superb in vivo nonhuman primate model of antigenic variation in malaria.

Antigenic variation in malaria was discovered in Plasmodium knowlesi studies involving longitudinal infections of rhesus macaques (M. mulatta). The variant proteins, known as the P. knowlesi Schizont Infected Cell Agglutination (SICA) antigens and the P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1) antigens, expressed by the SICAvar and var multigene families, respectively, have been studied for over 30 years. Expression of the SICA antigens in P. knowlesi requires a splenic component, and specific antibodies are necessary for variant antigen switch events in vivo. Outstanding questions revolve around the role of the spleen and the mechanisms by which the expression of these variant antigen families are regulated. Importantly, the longitudinal dynamics and molecular mechanisms that govern variant antigen expression can be studied with P. knowlesi infection of its mammalian and vector hosts. Synchronous infections can be initiated with established clones and studied at multi-omic levels, with the benefit of computational tools from systems biology that permit the integration of datasets and the design of explanatory, predictive mathematical models. Here we provide an historical account of this topic, while highlighting the potential for maximizing the use of P. knowlesi - macaque model systems and summarizing exciting new progress in this area of research

Salt marsh ecosystem biogeochemical responses to nutrient enrichment: a paired N-15 tracer study

We compared processing and fate of dissolved NO3- in two New England salt marsh ecosystems, one receiving natural flood tide concentrations of similar to 1-4 mu mol NO3-/L and the other receiving experimentally fertilized flood tides containing similar to 70-100 mu mol NO3-/L. We conducted simultaneous (NO3-)-N-15 (isotope) tracer additions from 23 to 28 July 2005 in the reference (8.4 ha) and fertilized (12.4 ha) systems to compare N dynamics and fate. Two full tidal cycles were intensively studied during the paired tracer additions. Resulting mass balances showed that essentially 100% (0.48-0.61 mol NO3-N.ha(-1).h(-1)) of incoming NO3- was assimilated, dissimilated, sorbed, or sedimented (processed) within a few hours in the reference system when NO3- concentrations were 1.3-1.8 mu mol/L. In contrast, only 50-60% of incoming NO3- was processed in the fertilized system when NO3- concentrations were 84-96 mu mol/ L; the remainder was exported in ebb tidewater. Gross NO3- processing was similar to 40 times higher in the fertilized system at 19.34- 24.67 mol NO3-N.ha(-1).h(-1). Dissimilatory nitrate reduction to ammonium was evident in both systems during the first 48 h of the tracer additions but \u3c1% of incoming (NO3-)-N-15 was exported as (NH4+)-N-15. Nitrification rates calculated by (NO3-)-N-15 dilution were 6.05 and 4.46 mol.ha(-1).h(-1) in the fertilized system but could not be accurately calculated in the reference system due to rapid (\u3c4 h) NO3- turnover. Over the five-day paired tracer addition, sediments sequestered a small fraction of incoming NO3-, although the efficiency of sequestration was 3.8% in the reference system and 0.7% in the fertilized system. Gross sediment N sequestration rates were similar at 13.5 and 12.6 mol.ha(-1).d(-1), respectively. Macrophyte NO3- uptake efficiency, based on tracer incorporation in aboveground tissues, was considerably higher in the reference system (16.8%) than the fertilized system (2.6%), although bulk uptake of NO3- by plants was lower in the reference system (1.75 mol NO3-.ha(-1).d(-1)) than the fertilized system (similar to 10 mol NO3-.ha(-1).d(-1)). Nitrogen processing efficiency decreased with NO3- load in all pools, suggesting that the nutrient processing capacity of the marsh ecosystem was exceeded in the fertilized marsh

Ecologic and Geographic Distribution of Filovirus Disease

We used ecologic niche modeling of outbreaks and sporadic cases of filovirus-associated hemorrhagic fever (HF) to provide a large-scale perspective on the geographic and ecologic distributions of Ebola and Marburg viruses. We predicted that filovirus would occur across the Afrotropics: Ebola HF in the humid rain forests of central and western Africa, and Marburg HF in the drier and more open areas of central and eastern Africa. Most of the predicted geographic extent of Ebola HF has been observed; Marburg HF has the potential to occur farther south and east. Ecologic conditions appropriate for Ebola HF are also present in Southeast Asia and the Philippines, where Ebola Reston is hypothesized to be distributed. This first large-scale ecologic analysis provides a framework for a more informed search for taxa that could constitute the natural reservoir for this virus family

Nucleosome repositioning via loop formation

Active (catalysed) and passive (intrinsic) nucleosome repositioning is known to be a crucial event during the transcriptional activation of certain eucaryotic genes. Here we consider theoretically the intrinsic mechanism and study in detail the energetics and dynamics of DNA-loop-mediated nucleosome repositioning, as previously proposed by Schiessel et al. (H. Schiessel, J. Widom, R. F. Bruinsma, and W. M. Gelbart. 2001. {\it Phys. Rev. Lett.} 86:4414-4417). The surprising outcome of the present study is the inherent nonlocality of nucleosome motion within this model -- being a direct physical consequence of the loop mechanism. On long enough DNA templates the longer jumps dominate over the previously predicted local motion, a fact that contrasts simple diffusive mechanisms considered before. The possible experimental outcome resulting from the considered mechanism is predicted, discussed and compared to existing experimental findings

Programmatic Environmental Scans: A Survey Based on Program Planning and Evaluation Concepts

Within Extension, environmental scans are most commonly used to assess community or organizational issues or for strategic planning purposes. However, Extension has expanded the use of environmental scans to systematically identify “what programs exist” on a given topic or focus area. Yet, despite recent attention to the topic of environmental scanning in Extension, survey instruments used to conduct environmental scans have not been published. Given the emphasis on implementation of evidence-based practices and programs, having a ready-made survey that can be used to identify programs on a specific topic and that could subsequently lead to an evaluability assessment of those programs would be a useful resource. To encourage the use of environmental scans to identify existing evidence-based programs, this article describes a survey instrument developed for the purpose of scanning for 4-H Healthy Living programs ready for rigorous outcome evaluation and/or national replication. It focuses on the rationale for survey items, as well as provides a summary and definition of those items. The survey tool can be easily adapted for future programmatic environmental scans both within and outside Extension

Municipal investment in off-road trails and changes in bicycle commuting in Minneapolis, Minnesota over 10 years: a longitudinal repeated cross-sectional study

Abstract Background We studied the effect of key development and expansion of an off-road multipurpose trail system in Minneapolis, Minnesota between 2000 and 2007 to understand whether infrastructure investments are associated with increases in commuting by bicycle. Methods We used repeated measures regression on tract-level (N = 116 tracts) data to examine changes in bicycle commuting between 2000 and 2008–2012. We investigated: 1) trail proximity measured as distance from the trail system and 2) trail potential use measured as the proportion of commuting trips to destinations that might traverse the trail system. All analyses (performed 2015–2016) adjusted for tract-level sociodemographic covariates and contemporaneous cycling infrastructure changes (e.g., bicycle lanes). Results Tracts that were both closer to the new trail system and had a higher proportion of trips to destinations across the trail system experienced greater 10-year increases in commuting by bicycle. Conclusions Proximity to off-road infrastructure and travel patterns are relevant to increased bicycle commuting, an important contributor to overall physical activity. Municipal investment in bicycle facilities, especially off-road trails that connect a city’s population and its employment centers, is likely to lead to increases in commuting by bicycle