The N-end rule pathway is a sensor of heme

The conjugation of arginine, by arginyl-transferase, to N-terminal aspartate, glutamate or oxidized cysteine is a part of the N-end rule pathway of protein degradation. We report that arginyl-transferase of either the mouse or the yeast Saccharomyces cerevisiae is inhibited by hemin (Fe3+-heme). Furthermore, we show that hemin inhibits arginyl-transferase through a redox mechanism that involves the formation of disulfide between the enzyme's Cys-71 and Cys-72 residues. Remarkably, hemin also induces the proteasome-dependent degradation of arginyl-transferase in vivo, thus acting as both a "stoichiometric" and "catalytic" down-regulator of the N-end rule pathway. In addition, hemin was found to interact with the yeast and mouse E3 ubiquitin ligases of the N-end rule pathway. One of substrate-binding sites of the yeast N-end rule's ubiquitin ligase UBR1 targets CUP9, a transcriptional repressor. This site of UBR1 is autoinhibited but can be allosterically activated by peptides that bear destabilizing N-terminal residues and interact with two other substrate-binding sites of UBR1. We show that hemin does not directly occlude the substrate-binding sites of UBR1 but blocks the activation of its CUP9-binding site by dipeptides. The N-end rule pathway, a known sensor of short peptides, nitric oxide, and oxygen, is now a sensor of heme as well. One function of the N-end rule pathway may be to coordinate the activities of small effectors, both reacting to and controlling the redox dynamics of heme, oxygen, nitric oxide, thiols, and other compounds, in part through conditional degradation of specific transcription factors and G protein regulators

Students with Asperger's Syndrome in General Education Classrooms

Thank you to Jeanne Sept, Dean of Faculties,and Dean Geraldo Gonzalez and Sarah Baumgart at the School of Education, Indiana University.Since the 1980's the number of students with Asperger's Syndrome (AS) have been seen in larger numbers in the general education classroom. Children with AS may resemble their counterparts without disabilities both physically and in IQ scores. However, students with AS have significant differences in social skills and their ability to function in the general classroom. Often unable to decipher social cues, verbal cues, and body language, these children are considered social outcasts. Regardless of the characteristics of children with AS, educators are required by law, specifically the Individuals with Disabilities Education Act (IDEA), to provide a free and appropriate public education. This article provides characteristics of AS and evidence-based interventiosn teachers can implement in their general classrooms to help educate students with AS.Dean of Faculties Office and the School of Education, Indiana Universit

A State Equalization Fund For Secondary Education

The problem of this study is: (1) to develop the present financial status of high schools in Kansas, (2) to present reasons for creating a state equalization fund for high schools in Kansas, (3) to briefly study plans for the equalization of public education now in operation in certain selected states, and (4) to propose a plan whereby the burden of support and the educational advantages of a minimum high school program will be equalized

Shattering the Crystal Goblet: Seeking a Pedagogy of Visuality in Post - Typographic Expository Texts

This article synthesizes diverse theoretical perspectives toward developing a pedagogy that addresses the visuality of digital texts. To frame those perspectives and their implications, I use a well - known analogy that Beatrice Warde introduced to typographers in the 1930s: drinking wine from a golden cup or a crystal goblet. I briefly review the theory and research related to visual aspects of texts, generating pedagogical perspectives from several prominent theories and perspectives. I then discuss, illustrated with a few examples, how these pedagogical perspectives might be instantiated in curriculum and instruction and the issues and challenges of doing so. I argue that researchers have done little to directly address those challenges and issues in ways that inform practitioners

Pallid bands in feathers and associated stable isotope signatures reveal effects of severe weather stressors on fledgling sparrows

Citation: Ross, J. D., Kelly, J. F., Bridge, E. S., Engel, M. H., Reinking, D. L., & Boyle, W. A. (2015). Pallid bands in feathers and associated stable isotope signatures reveal effects of severe weather stressors on fledgling sparrows. Peerj, 3, 21. doi:10.7717/peerj.814In August 2013, we observed a high incidence (44%) of synchronous bands of reduced melanin (a type of fault bar we have termed "pallid bands") across the rectrices of juvenile Grasshopper Sparrows (Ammodrammus savannarum) captured near El Reno, Oklahoma. Earlier that year, on May 31, the site was struck by a severe storm which rained hailstones exceeding 5.5 cm diameter and spawned an historic 4.2 km-wide tornado <8 km to the south of the site. We hypothesized that this stressor had induced the pallid bands. An assessment of Grasshopper Sparrow nesting phenology indicated that a large number of nestlings were likely growing tail feathers when the storm hit. The pallid bands were restricted to the distal half of feathers and their widths significantly increased as a function of distance from the tip (i.e., age at formation). We predicted that if stress had caused these pallid bands, then a spike in circulating delta N-15 originating from tissue catabolism during the stress response would have been incorporated into the developing feather. From 18 juveniles captured at the site in August we measured delta N-15 and delta C-13 stable isotope ratios within four to five 0.25-0.40 mg feather sections taken from the distal end of a tail feather; the pallid band, if present, was contained within only one section. After accounting for individual and across-section variation, we found support for our prediction that feather sections containing or located immediately proximal to pallid bands (i.e., the pallid band region) would show significantly higher delta N-15 than sections outside this region. In contrast, the feathers of juveniles with pallid bands compared to normal appearing juveniles showed significantly lower delta N-15. A likely explanation is that the latter individuals hatched after the May 31 storm and had consumed a trophically-shifted diet relative to juveniles with pallid bands. Considering this, the juveniles of normal appearance were significantly less abundant within our sample relative to expectations from past cohorts (z = -2.03; p = 0.042) and, in as much, suggested widespread nest losses during the storm. Severe weather events may represent major stressors to ground-nesting birds, especially for recent fledglings. We call for others to exploit opportunities to study the effects of severe weather when these rare but devastating stressors impact established field research sites

A Performance Improvement Nursing Fellowship to Enhance Timely Access to Care

This scholarly report describes a Doctorate of Nursing Practice (DNP) project that advanced the performance improvement (PI) knowledge of frontline nurses to improve timely access to acute care during a 6-month PI/Lean management nursing fellowship. Patient flow issues delay access to care and result in negative patient quality outcomes and safety failures. Patient experience, confidence, and satisfaction in healthcare organizations erode when timeliness and efficiency are deficient. The project site is a 443-bed, two-campus, not for profit community hospital in Northern California. This project included the implementation of a PI/Lean nursing fellowship program as an evidence-based intervention to address patient flow issues. During the project, the nurse fellows were expected to learn through didactic education in addition to engaging, integrating, and leading PI/Lean activities within the organization. Patient flow measurements occurred six months before and during the fellowship. PI/Lean knowledge and skills acquisition were measured using a pre- and post-knowledge assessment tool. A program effectiveness survey was administered to team members. A qualitative survey gauged the fellowship’s impact. The timeliness of access to care indicated a degradation of 5 minutes or 2% during the entire 6-month fellowship though a 3-minute improvement occurred in the final three months. The fellows’ pre- and post-assessment indicated a 60% improvement. The fellowship effectiveness survey indicated an 83% satisfaction rate. The qualitative survey revealed a positive tone. The nursing fellowship provided a methodology to advance the frontline nurses’ knowledge and skills in improvement science while assisting the organization in achieving a priority strategic initiative