Ribosomal trafficking is reduced in Schwann cells following induction of myelination.

Local synthesis of proteins within the Schwann cell periphery is extremely important for efficient process extension and myelination, when cells undergo dramatic changes in polarity and geometry. Still, it is unclear how ribosomal distributions are developed and maintained within Schwann cell projections to sustain local translation. In this multi-disciplinary study, we expressed a plasmid encoding a fluorescently labeled ribosomal subunit (L4-GFP) in cultured primary rat Schwann cells. This enabled the generation of high-resolution, quantitative data on ribosomal distributions and trafficking dynamics within Schwann cells during early stages of myelination, induced by ascorbic acid treatment. Ribosomes were distributed throughout Schwann cell projections, with ~2-3 bright clusters along each projection. Clusters emerged within 1 day of culture and were maintained throughout early stages of myelination. Three days after induction of myelination, net ribosomal movement remained anterograde (directed away from the Schwann cell body), but ribosomal velocity decreased to about half the levels of the untreated group. Statistical and modeling analysis provided additional insight into key factors underlying ribosomal trafficking. Multiple regression analysis indicated that net transport at early time points was dependent on anterograde velocity, but shifted to dependence on anterograde duration at later time points. A simple, data-driven rate kinetics model suggested that the observed decrease in net ribosomal movement was primarily dictated by an increased conversion of anterograde particles to stationary particles, rather than changes in other directional parameters. These results reveal the strength of a combined experimental and theoretical approach in examining protein localization and transport, and provide evidence of an early establishment of ribosomal populations within Schwann cell projections with a reduction in trafficking following initiation of myelination

Historical contingency and entrenchment in protein evolution under purifying selection

The fitness contribution of an allele at one genetic site may depend on alleles at other sites, a phenomenon known as epistasis. Epistasis can profoundly influence the process of evolution in populations under selection, and can shape the course of protein evolution across divergent species. Whereas epistasis between adaptive substitutions has been the subject of extensive study, relatively little is known about epistasis under purifying selection. Here we use mechanistic models of thermodynamic stability in a ligand-binding protein to explore the structure of epistatic interactions between substitutions that fix in protein sequences under purifying selection. We find that the selection coefficients of mutations that are nearly-neutral when they fix are highly contingent on the presence of preceding mutations. Conversely, mutations that are nearly-neutral when they fix are subsequently entrenched due to epistasis with later substitutions. Our evolutionary model includes insertions and deletions, as well as point mutations, and so it allows us to quantify epistasis within each of these classes of mutations, and also to study the evolution of protein length. We find that protein length remains largely constant over time, because indels are more deleterious than point mutations. Our results imply that, even under purifying selection, protein sequence evolution is highly contingent on history and so it cannot be predicted by the phenotypic effects of mutations assayed in the wild-type sequence.Comment: 42 pages, 13 figure

Scaling and Formulary cross sections for ion-atom impact ionization

The values of ion-atom ionization cross sections are frequently needed for many applications that utilize the propagation of fast ions through matter. When experimental data and theoretical calculations are not available, approximate formulas are frequently used. This paper briefly summarizes the most important theoretical results and approaches to cross section calculations in order to place the discussion in historical perspective and offer a concise introduction to the topic. Based on experimental data and theoretical predictions, a new fit for ionization cross sections is proposed. The range of validity and accuracy of several frequently used approximations (classical trajectory, the Born approximation, and so forth) are discussed using, as examples, the ionization cross sections of hydrogen and helium atoms by various fully stripped ions.Comment: 46 pages, 8 figure

Participatory Ranking of Fodders in the Western Hills of Nepal

Fodder is an important source of feed of the ruminants in Nepal. In the mid hills of Nepal, farmers generally practice integrated farming system that combines crop cultivation with livestock husbandry and agroforestry. Tree fodders are good sources of protein during the forage and green grass scarcity periods especially in dry season. Local communities possess indigenous knowledge for the selection of grasses and tree fodders at different seasons in mid hills of western Nepal. A study was conducted on the perception of farmers with respect to selection of fodder species in eight clusters in Kaski and Lumjung districts that range 900-2000 meter above sea level and receive average precipitation of 2000- 4500mm per annum. During the fodder preference ranking, farmers prepared the inventory of fodders found around the villages and nearby forests and selected top ten most important fodders in terms of their availability, palatability, fodder yield, milk yield and milk fat yield. In total, 23 top ranking fodders species were selected from the eight clusters. These fodder species were also ranked using pairwise ranking and weighted scoring methods and ranking was done on the basis of merit numbers obtained from weighted scores. The analysis revealed Artocarpus lakoocha as best tree fodder followed by Ficus semicordata, Thysanolena maxima and Ficus calvata. Similarly, the calendar of fodders trees for lopping season and the best feeding time was prepared on the basis of farmers\u27 local knowledge. This study suggests strategies for promotion of locally preferred tree fodder species and supplementing tree fodder with feed in different seasons depending on their availability and local preferences

High Bandwidth Atomic Magnetometery with Continuous Quantum Non-demolition Measurements

We describe an experimental study of spin-projection noise in a high sensitivity alkali-metal magnetometer. We demonstrate a four-fold improvement in the measurement bandwidth of the magnetometer using continuous quantum non-demolition (QND) measurements. Operating in the scalar mode with a measurement volume of 2 cm^3 we achieve magnetic field sensitivity of 22 fT/Hz^(1/2) and a bandwidth of 1.9 kHz with a spin polarization of only 1%. Our experimental arrangement is naturally back-action evading and can be used to realize sub-fT sensitivity with a highly polarized spin-squeezed atomic vapor.Comment: 4 page