Ab initio molecular dynamics calculations of ion hydration free energies

We apply ab initio molecular dynamics (AIMD) methods in conjunction with the thermodynamic integration or "lambda-path" technique to compute the intrinsic hydration free energies of Li+, Cl-, and Ag+ ions. Using the Perdew-Burke-Ernzerhof functional, adapting methods developed for classical force field applications, and with consistent assumptions about surface potential (phi) contributions, we obtain absolute AIMD hydration free energies (Delta G(hyd)) within a few kcal/mol, or better than 4%, of Tissandier 's [J. Phys. Chem. A 102, 7787 (1998)] experimental values augmented with the SPC/E water model phi predictions. The sums of Li+/Cl- and Ag+/Cl- AIMD Delta G(hyd), which are not affected by surface potentials, are within 2.6% and 1.2 % of experimental values, respectively. We also report the free energy changes associated with the transition metal ion redox reaction Ag++Ni+-> Ag+Ni2+ in water. The predictions for this reaction suggest that existing estimates of Delta G(hyd) for unstable radiolysis intermediates such as Ni+ may need to be extensively revised.Comment: 18 pages, 8 figures. This version is essentially the one published in J. Chem. Phy

Rabies serology: relationship between assay type, interpretation, and application of results

Doctor of PhilosophyDepartment of Diagnostic Medicine/PathobiologyElizabeth DavisThe immune status of an individual host or among a population is affected by important variables including the source and route of potential natural exposure and for vaccination consist of vaccine type, potency, and virus strain; vaccination route and schedule; and individual host factors. Although, perhaps, often overlooked, it is essential to have a basic understanding of the laboratory methods used to measure and assess the host’s immune status. The precision, accuracy, sensitivity, and specificity of a method must be well defined. Moreover, an “adequate,” acceptable, or diagnostic value for each method must be clearly defined so that a particular test result for a patient can be meaningfully interpreted in relation to the patient’s history and clinical management. The reasons for performing rabies serology can range from diagnosis of infection to investigation of epitope specificity of an anti-rabies virus glycoprotein monoclonal antibody. Characterization of an antibody’s affinity, specificity, quantity, and neutralizing function, and class/subclass are achieved by various methods. Many serological techniques developed over the past five decades differ not only in their ability to detect the function, affinity and specificity of rabies virus antibodies, but also in the ease and practicality with which they are performed. To select an appropriate method and appropriately interpret test results, it is essential to understand the specific strengths, weaknesses, and limitations of available methods. The decision to use a specific assay should start with the purpose of testing and the intended application of results. Other factors to consider are the assay complexity, degree of precision and/or accuracy, specificity and range of detection. Given the importance of RVNA levels in the prevention of human and animal rabies, guidelines for adequate vaccination should be stated in terms that are readily understood by individuals-at-risk and health care providers, both veterinary and medical, who will use the recommendations for clinical management of humans or animals. Across the globe, the standardization of rabies serologic assays has a direct effect on the clinical use of human and animal products, including direct assessment of, and assessment of host responses to, rabies vaccines for the prevention of rabies

Bayesian Spatiotemporal Pattern and Eco-climatological Drivers of Striped Skunk Rabies in the North Central Plains

Citation: Raghavan, R. K., Hanlon, C. A., Goodin, D. G., Davis, R., Moore, M., Moore, S., & Anderson, G. A. (2016). Bayesian Spatiotemporal Pattern and Eco-climatological Drivers of Striped Skunk Rabies in the North Central Plains. Plos Neglected Tropical Diseases, 10(4), 16. doi:10.1371/journal.pntd.0004632Striped skunks are one of the most important terrestrial reservoirs of rabies virus in North America, and yet the prevalence of rabies among this host is only passively monitored and the disease among this host remains largely unmanaged. Oral vaccination campaigns have not efficiently targeted striped skunks, while periodic spillovers of striped skunk variant viruses to other animals, including some domestic animals, are routinely recorded. In this study we evaluated the spatial and spatio-temporal patterns of infection status among striped skunk cases submitted for rabies testing in the North Central Plains of US in a Bayesian hierarchical framework, and also evaluated potential eco-climatological drivers of such patterns. Two Bayesian hierarchical models were fitted to point-referenced striped skunk rabies cases [n = 656 (negative), and n = 310 (positive)] received at a leading rabies diagnostic facility between the years 2007-2013. The first model included only spatial and temporal terms and a second covariate model included additional covariates representing eco-climatic conditions within a 4km(2) home-range area for striped skunks. The better performing covariate model indicated the presence of significant spatial and temporal trends in the dataset and identified higher amounts of land covered by low-intensity developed areas [Odds ratio (OR) = 3.41; 95% Bayesian Credible Intervals (CrI) = 2.08, 3.85], higher level of patch fragmentation (OR = 1.70; 95% CrI = 1.25, 2.89), and diurnal temperature range (OR = 0.54; 95% CrI = 0.27, 0.91) to be important drivers of striped skunk rabies incidence in the study area. Model validation statistics indicated satisfactory performance for both models; however, the covariate model fared better. The findings of this study are important in the context of rabies management among striped skunks in North America, and the relevance of physical and climatological factors as risk factors for skunk to human rabies transmission and the space-time patterns of striped skunk rabies are discussed

Magnesium-dependent Association and Folding of Oligonucleosomes Reconstituted with Ubiquitinated H2A

The MgCl2-induced folding of defined 12-mer nucleosomal arrays, in which ubiquitinated histone H2A (uH2A) replaced H2A, was analyzed by quantitative agarose gel electrophoresis and analytical centrifugation. Both types of analysis showed that uH2A arrays attained a degree of compaction similar to that of control arrays in 2 mM MgCl2. These results indicate that attachment of ubiquitin to H2A has little effect on the ability of nucleosomal arrays to form higher order folded structures in the ionic conditions tested. In contrast, uH2A arrays were found to oligomerize at lower MgCl2 concentrations than control nucleosomal arrays, suggesting that histone ubiquitination may play a role in nucleosomal fiber association

The influence of beta-1,3-1,6-glucans on rabies vaccination titers in cats

beta-glucans have been shown to stimulate the immune system in several animal species. The aim of this study was to evaluate the immune stimulation capacity of a fully formulated diet with beta-1,3-1,6-glucans in cats, by assessing the rabies antibody titer after vaccination. Thirty-five healthy cats were recruited. The cats were placed into two groups and fed a standard diet in accordance with body weight. One group had the beta-glucans incorporated into the diet; the other group served as the control group. After two weeks of dietary adjustment; the rabies vaccine (Imrab(R)3 TF; Merial) was administered on days 0 and 21. Blood samples were taken on days 0, 21, and 42. Titers were determined with the rapid fluorescent foci inhibition test (RFFIT). Titers at days 21 and 42 were compared between the two groups in a linear mixed effects model. This study showed that the animals receiving the non-supplemented feed had higher post-vaccination rabies antibody titers. This indicates that, in contrast to other animal species, the beta-glucan supplemented diet did not have the expected positive effect on the rabies antibody titers in cats

Integrating Emerging Areas of Nursing Science into PhD Programs

The Council for the Advancement of Nursing Science aims to “facilitate and recognize life-long nursing science career development” as an important part of its mission. In light of fast-paced advances in science and technology that are inspiring new questions and methods of investigation in the health sciences, the Council for the Advancement of Nursing Science convened the Idea Festival for Nursing Science Education and appointed the Idea Festival Advisory Committee to stimulate dialogue about linking PhD education with a renewed vision for preparation of the next generation of nursing scientists. Building on the 2010 American Association of Colleges of Nursing Position Statement “The Research-Focused Doctoral Program in Nursing: Pathways to Excellence,” Idea Festival Advisory Committee members focused on emerging areas of science and technology that impact the ability of research-focused doctoral programs to prepare graduates for competitive and sustained programs of nursing research using scientific advances in emerging areas of science and technology. The purpose of this article is to describe the educational and scientific contexts for the Idea Festival, which will serve as the foundation for recommendations for incorporating emerging areas of science and technology into research-focused doctoral programs in nursing

Emerging Areas of Science: Recommendations for Nursing Science Education from the Council for the Advancement of Nursing Science Idea Festival

The Council for the Advancement of Nursing Science aims to “facilitate and recognize life-long nursing science career development” as an important part of its mission. In light of fast-paced advances in science and technology that are inspiring new questions and methods of investigation in the health sciences, the Council for the Advancement of Nursing Science convened the Idea Festival for Nursing Science Education and appointed the Idea Festival Advisory Committee (IFAC) to stimulate dialogue about linking PhD education with a renewed vision for preparation of the next generation of nursing scientists. Building on the 2005 National Research Council report Advancing The Nation\u27s Health Needs and the 2010 American Association of Colleges of Nursing Position Statement on the Research-Focused Doctorate Pathways to Excellence, the IFAC specifically addressed the capacity of PhD programs to prepare nursing scientists to conduct cutting-edge research in the following key emerging and priority areas of health sciences research: omics and the microbiome; health behavior, behavior change, and biobehavioral science; patient-reported outcomes; big data, e-science, and informatics; quantitative sciences; translation science; and health economics. The purpose of this article is to (a) describe IFAC activities, (b) summarize 2014 discussions hosted as part of the Idea Festival, and (c) present IFAC recommendations for incorporating these emerging areas of science and technology into research-focused doctoral programs committed to preparing graduates for lifelong, competitive careers in nursing science. The recommendations address clearer articulation of program focus areas; inclusion of foundational knowledge in emerging areas of science in core courses on nursing science and research methods; faculty composition; prerequisite student knowledge and skills; and in-depth, interdisciplinary training in supporting area of science content and methods