Tissue-specific biochemical differences between chronic wasting disease prions isolated from free-ranging white-tailed deer (Odocoileus virginianus).

Chronic wasting disease (CWD) is an invariably fatal prion disease affecting cervid species worldwide. Prions can manifest as distinct strains that can influence disease pathology and transmission. CWD is profoundly lymphotropic, and most infected cervids likely shed peripheral prions replicated in lymphoid organs. However, CWD is a neurodegenerative disease, and most research on prion strains has focused on neurogenic prions. Thus, a knowledge gap exists comparing neurogenic prions to lymphogenic prions. In this study, we compared prions from the obex and lymph nodes of naturally exposed white-tailed deer to identify potential biochemical strain differences. Here, we report biochemical evidence of strain differences between the brain and lymph node from these animals. Conformational stability assays, glycoform ratio analyses, and immunoreactivity scanning across the structured domain of the prion protein that refolds into the amyloid aggregate of the infectious prion reveal significantly more structural and glycoform variation in lymphogenic prions than neurogenic prions. Surprisingly, we observed greater biochemical differences among neurogenic prions than lymphogenic prions across individuals. We propose that the lymphoreticular system propagates a diverse array of prions from which the brain selects a more restricted pool of prions that may be quite different than those from another individual of the same species. Future work should examine the biological and zoonotic impact of these biochemical differences and examine more cervids from multiple locations to determine if these differences are conserved across species and locations.

Ontogenetic survey of histone modifications in an annelid.

Histone modifications are widely recognized for their fundamental importance in regulating gene expression in embryonic development in a wide range of eukaryotes, but they have received relatively little attention in the development of marine invertebrates. We surveyed histone modifications throughout the development of a marine annelid, Polydora cornuta, to determine if modifications could be detected immunohistochemically and if there were characteristic changes in modifications throughout ontogeny (surveyed at representative stages from oocyte to adult). We found a common time of onset for three histone modifications in early cleavage (H3K14ac, H3K9me, and H3K4me2), some differences in the distribution of modifications among germ layers, differences in epifluorescence intensity in specific cell lineages suggesting that hyperacetylation (H3K14ac) and hypermethylation (H3K9me) occur during differentiation, and an overall decrease in the distribution of modifications from larvae to adults. Although preliminary, these results suggest that histone modifications are involved in activating early development and differentiation in a marine invertebrate.

Understanding decimal numbers: a foundation for correct calculations.

This paper reports on the effectiveness of an intervention designed to improve nursing students' conceptual understanding of decimal numbers. Results of recent intervention studies have indicated some success at improving nursing students' numeracy through practice in applying procedural rules for calculation and working in real or simulated practical contexts. However, in this we identified a fundamental problem: a significant minority of students had an inadequate understanding of decimal numbers. The intervention aimed to improve nursing students' basic understanding of the size of decimal numbers, so that, firstly, calculation rules are more meaningful, and secondly, students can interpret decimal numbers (whether digital output or results of calculations) sensibly. A well-researched, time-efficient diagnostic instrument was used to identify individuals with an inadequate understanding of decimal numbers. We describe a remedial intervention that resulted in significant improvement on a delayed post-intervention test. We conclude that nurse educators should consider diagnosing and, as necessary, plan for remediation of students' foundational understanding of decimal numbers before teaching procedural rules.