Exploiting macrophage autophagy-lysosomal biogenesis as a therapy for atherosclerosis

Macrophages specialize in removing lipids and debris present in the atherosclerotic plaque. However, plaque progression renders macrophages unable to degrade exogenous atherogenic material and endogenous cargo including dysfunctional proteins and organelles. Here we show that a decline in the autophagy-lysosome system contributes to this as evidenced by a derangement in key autophagy markers in both mouse and human atherosclerotic plaques. By augmenting macrophage TFEB, the master transcriptional regulator of autophagy-lysosomal biogenesis, we can reverse the autophagy dysfunction of plaques, enhance aggrephagy of p62-enriched protein aggregates and blunt macrophage apoptosis and pro-inflammatory IL-1β levels, leading to reduced atherosclerosis. In order to harness this degradative response therapeutically, we also describe a natural sugar called trehalose as an inducer of macrophage autophagy-lysosomal biogenesis and show trehalose's ability to recapitulate the atheroprotective properties of macrophage TFEB overexpression. Our data support this practical method of enhancing the degradative capacity of macrophages as a therapy for atherosclerotic vascular disease

Efficient intra- and inter-night linking of asteroid detections using kd-trees

The Panoramic Survey Telescope And Rapid Response System (Pan-STARRS) under development at the University of Hawaii's Institute for Astronomy is creating the first fully automated end-to-end Moving Object Processing System (MOPS) in the world. It will be capable of identifying detections of moving objects in our solar system and linking those detections within and between nights, attributing those detections to known objects, calculating initial and differentially-corrected orbits for linked detections, precovering detections when they exist, and orbit identification. Here we describe new kd-tree and variable-tree algorithms that allow fast, efficient, scalable linking of intra and inter-night detections. Using a pseudo-realistic simulation of the Pan-STARRS survey strategy incorporating weather, astrometric accuracy and false detections we have achieved nearly 100% efficiency and accuracy for intra-night linking and nearly 100% efficiency for inter-night linking within a lunation. At realistic sky-plane densities for both real and false detections the intra-night linking of detections into `tracks' currently has an accuracy of 0.3%. Successful tests of the MOPS on real source detections from the Spacewatch asteroid survey indicate that the MOPS is capable of identifying asteroids in real data.Comment: Accepted to Icaru

Natural Variation of Fructose-1,6-Bisphosphatase in \u3ci\u3eColias\u3c/i\u3e Butterflies

In a process known as the evolutionary recursion, it is possible to follow how adaptation affects natural selection at successive stages of a species’ life cycle. Through studying allele and genotype frequencies of enzymes in glycolysis, a central metabolic pathway, it is possible to document how polymorphisms can shift the evolving functionality of enzymes within or among species. Fructose-1,6-bisphosphatase (FBPase) is an enzyme in gluconeogenesis that converts fructose-1,6-bisphosphate to fructose 6- phosphate. It is also known to convert the unused amino acid carbon skeletons of glycolysis into glycogen storage. Appearing to play a vital role in the acquisition, storage, and redistribution of carbon skeleton resources derived from larval feeding throughout an individual’s lifetime, FBPase could be influential in adaptation leading to diverging life history strategies. FBPase from seven isolated populations of North American Colias butterflies (four C. meadii, two C. eriphyle, and one C. eurytheme) were sequenced. Within C. meadii, we sampled on an elevational gradient both above and below tree line. We first tested the neutral null hypothesis that states any present genetic variation will be neutral. FBPase variation is not neutral, and once the null was violated, we hypothesized that a.) there will be a decrease in FBPase variation as elevation increases within species and b.) there will be a positive phylogentic correlation to variation among species. Strong purifying selection is acting on FBPase nonsynonymous variants. Based on a linear regression, elevation does not have an effect on FBPase variation within C. meadii. Among species, there is no positive phylogenetic correlation to FBPase variation. While initially surprising, the lack of a phylogenetic relationship between Colias and FBPase variation now allows for questions to be asked about varying life history strategies that also do not follow phylogenetic relationships. By studying the genetic variation of FBPase, in combination with future field studies, we will be able to directly relate genotypes to performance

What do we teach when we teach the Learning Sciences? A document analysis of 75 graduate programs

The learning sciences, as an academic community investigating human learning, emerged more than 30 years ago. Since then, graduate learning sciences programs have been established worldwide. Little is currently known, however, about their disciplinary backgrounds and the topics and research methods they address. In this document analysis of the websites of 75 international graduate learning sciences programs, we examine central concepts and research methods across institutions, compare the programs, and assess the homogeneity of different subgroups. Results reveal that the concepts addressed most frequently were real-world learning in formal and informal contexts, designing learning environments, cognition and metacognition, and using technology to support learning. Among research methods, design-based research (DBR), discourse and dialog analyses, and basic statistics stand out. Results show substantial differences between programs, yet programs focusing on DBR show the greatest similarity regarding the other concepts and methods they teach. Interpreting the similarity of the graduate programs using a community of practice perspective, there is a set of relatively coherent programs at the core of the learning sciences, pointing to the emergence of a discipline, and a variety of multidisciplinary and more heterogeneous programs “orbiting” the core in the periphery, shaping and innovating the field

Editorial: special issues in Business History

No abstract available

Editorial

With the first issue of the 56th volume of Business History, a new editorial team has taken over responsibility for direction and management of the journal. Led by executive editor Ray Stokes (University of Glasgow), the team includes as co-editors Andrea Colli (Bocconi University), Stephanie Decker (Aston University), Paloma Fernández Pérez (University of Barcelona), Abe de Jong (Erasmus University Rotterdam) and Neil Rollings (University of Glasgow), who will also serve as deputy editor. In addition, the book review editorship has been expanded. Joining Kevin Tennent (York University), who has acted as sole book review editor over the past years, will be Veronica Binda (Bocconi University). Veronica Binda will be primarily responsible for books published in, or reviewed by, authors from Italy, Spain, France, and Portugal

Observations on questing activity of adult Gulf Coast ticks, Amblyomma maculatum

Abstract During August of 2008 and 2009, observations were made on the questing heights, behaviors, and spatial distribution of adult Gulf Coast ticks, Amblyomma maculatum, in a plot near Gautier, Jackson County, Mississippi, U.S.A. Ticks were not evenly distributed in the plot, being found mostly on torpedograss and/or wiregrass along and in a small dirt field road. Adult ticks were visually observed questing on three different plants: torpedograss, Panicum repens, wiregrass, Aristida stricta, and Johnsongrass, Sorghum halepense, all but the last of which have small-diameter stems and thin, pointed leaves. Ticks were located at or near the tips of the plants (2-tail binomial probability, p = 0.0074). Observed questing heights ranged from 20-75 cm, with an average of 36 cm. Nine of 15 ticks (60%) seen questing were oriented head upward, while 6 (40%) were headdown. Limited mark-release-recapture observations were made in the study site, using ticks collected from the field road. Of 27 ticks marked and released, 15 were recaptured in three samples spanning a 24-d period. Of these, 5 had moved closer to the dirt road where they were originally captured and 2 farther away