The Grizzly, February 26, 2004

The Whites-Only Scholarship Spurs Nationwide Controversy • Harvard Strips Down and Bares all • UC Presents Vagina Monologues Next Week • Spotlight on Kerry and Edwards • In Memory of James C. Wilkes, Jr. • Opinions: Bush\u27s Big Bungle; Do Students Work?; Mel Gibson\u27s The Passion of the Christ: Worth the Controversy?; A Bearable V-Day at Fox and Hound • Men\u27s Basketball Fighting Their Way to the Playoffs • Wrestling Team Dominates the Conference • Grimmel Named ECAC Division III Gymnast of the Year • Letter to the Editors: Sports Coverage Concernshttps://digitalcommons.ursinus.edu/grizzlynews/1555/thumbnail.jp

The Grizzly, April 8, 2004

Students Find a New Way to Connect • Democrats Club Active in Upcoming Elections • Ursinus and USGA: Who We Are • The 9/11 Investigation: Rice vs. Clarke • Opinions: Unhappy Happy Hour ; UC Chess Tournament; Dine Like the Irish at Kildare\u27s • Student Spotlight: Sarah Kauffman Exposed • Save the Speaker\u27s House • Pew Lecture: Peter Rose Hypnotizes Students with his Work • Young Nucleus Coming Together for UC Men\u27s Lacrosse • Women\u27s Lacrosse Working to Keep Season Alive • Women\u27s Rugby Hanging in Toughhttps://digitalcommons.ursinus.edu/grizzlynews/1558/thumbnail.jp

Quantifying ubiquitin dynamics

2019 Fall.Includes bibliographical references.Ubiquitin (Ub) is a small protein that is frequently attached to other proteins as a post-translational modification (PTM) to elicit a new function, cellular localization, or otherwise modulate the activity of the substrate protein. Ub addition and removal serves as a signal for proteasome degradation, regulation of cell division, gene expression, membrane and protein trafficking and signaling in a multitude of stress response mechanisms. Defects in ubiquitination or deubiquitination have been linked to cancer onset and progression, muscle dystrophies, and disorders in inflammation and immunity; these findings further highlight the critical processes regulated by Ub. Due to its high demand, cellular Ub levels are highly regulated, such that the abundance of free Ub is above a threshold enabling new ubiquitination events, a critical part of normal cell function and survival. Due to the high demand on the cellular free Ub pool to supply substrate for thousands of ubiquitination reactions, it is tightly regulated in many ways. Our knowledge of Ub homeostasis has not advanced, likely due to the lack of accurate, sensitive methods for pool quantitation that can be performed routinely. Here, a method is presented that utilizes a high affinity free Ub binding protein to quantify cellular pools of Ub after a series of treatment protocols. The methods can be performed within a day and are amenable to high throughput applications. Using these methods, the Ub pool distributions of cells under conditions such as proteasome inhibitor and heat stress were assessed. However, this assay will only report the steady-state concentration of Ub in each pool; it provides no information about the rate of movement through them. The rates of competing ubiquitination and deubiquitination or degradation reactions determine the steady-state level of every Ub-protein conjugate; however, measurement of the rate of Ub movement these conjugates remains a challenge. Thus, the relative contributions of conjugation and disassembly rates in cellular responses to different signals are rarely known. Moreover, even though the concentration of a particular Ub-protein conjugate may appear unchanged, the flux of Ub through that conjugate might change dramatically. To address these deficits in our understanding of ubiquitination, we have developed a method to label Ub and follow its movement through conjugation pathways that we call SILOW or Stable Isotope Labeling with ¹⁸O-Water. Our method is applicable to both yeast and mammalian cells, does not perturb cellular physiology in any way and can be used with conventional proteomics methods. SILOW permits rapid changes in Ub flux to be evaluated over short times across hundreds of sites within the human cell proteome to reveal the intracellular dynamics of Ub-conjugation in specific Ub-Ub linkages of polyUb compared with Ub-protein linkages of histones

Comparing the GLP-1 Receptor Agonists: Byetta®, Victoza® and once-weekly Bydureon™

Type 2 diabetes mellitus (T2DM) has traditionally been managed with oral medications. However, in the last few years, subcutaneous glucagon-like peptide-1 (GLP-1) receptor agonists have risen to fame. These agents serve as a reliable addition to current monotherapy. GLP-1 receptor agonists offer a significant reduction in hemoglobin AlC (HbAlc), fasting plasma glucose, and have the added benefit of weight loss. They work primarily by enhancing glucose-dependent insulin secretion while inhibiting glucagon secretion. The available GLP-1 agonists are Byetta® (exenatide), Victoza® (liraglutide), and Bydureon™ (exenatide extended-release). Studies suggest that they are similar in safety and efficacy, with the longer acting GLP-1 receptor agonists, liraglutide and extended-release exenatide, proving to be slightly more efficacious in terms of HbAlc and weight reduction. All three products have unique half-lives, dosing schedules, efficacies, side effects and contraindications

Developing an Assessment Framework for Essential Internal Medicine Subspecialty Topics

Assessing residents by direct observation is the preferred assessment method for infrequently encountered subspecialty topics, but this is logistically challenging. We developed an assessment framework for internal medicine (IM) residents in subspecialty topics, using tuberculosis diagnosis for proof of concept. We used a 4-step process at 8 academic medical centers that entailed (1) creating a 10-item knowledge assessment tool; (2) pilot testing on a sample of 129 IM residents and infectious disease fellow volunteers to evaluate validity evidence; (3) implementing the final tool among 886 resident volunteers; and (4) assessing outcomes via retrospective chart review. Outcomes included tool score, item performance, and rates of obtaining recommended diagnostics. Following tool development, 10 infectious disease experts provided content validity. Pilot testing showed higher mean scores for fellows compared with residents (7 [SD = 1.8] versus 3.8 [SD = 1.7], respectively,  < .001) and a satisfactory Kuder-Richardson Formula 20 (0.72). Implementation of the tool revealed a 14-minute (SD = 2.0) mean completion time, 61% (541 of 886) response rate, 4.4 (SD = 1.6) mean score, and ≤ 57% correct response rate for 9 of 10 items. On chart review (n = 343), the rate of obtaining each recommended test was ≤ 43% (113 of 261), except for chest x-rays (96%, 328 of 343). Our assessment framework revealed knowledge and practice gaps in tuberculosis diagnosis in IM residents. Adopting this approach may help ensure assessment is not limited to frequently encountered topics

Internal Medicine Residents’ Knowledge and Practice of Pulmonary Tuberculosis Diagnosis

Abstract Background Internal medicine physicians are often the first providers to encounter patients with a new diagnosis of tuberculosis. Given the public health risks of missed tuberculosis cases, assessing internal medicine residents’ ability to diagnose tuberculosis is important. Methods Internal medicine resident knowledge and practice patterns in pulmonary tuberculosis diagnosis at 7 academic hospitals were assessed utilizing (a) a 10-item validated pulmonary tuberculosis diagnosis assessment tool and (b) a retrospective chart review of 343 patients who underwent a pulmonary tuberculosis evaluation while admitted to a resident-staffed internal medicine or infectious disease service. Our primary outcomes were the mean score and percentage of correct responses per assessment tool question, and the percentage of patients who had Centers for Disease Control and Prevention–recommended tuberculosis diagnostic tests obtained. Results Of the 886 residents who received the assessment, 541 responded, yielding a response rate of 61%. The mean score on the assessment tool (SD) was 4.4 (1.6), and the correct response rate was 57% (311/541) or less on 9 of 10 questions. On chart review, each recommended test was obtained for ≤43% (148/343) of patients, other than chest x-ray (328/343; 96%). A nucleic acid amplification test was obtained for 18% (62/343) of patients, whereas 24% (83/343) had only 1 respiratory sample obtained. Twenty patients were diagnosed with tuberculosis. Conclusions Significant knowledge and practice gaps exist in internal medicine residents’ abilities to diagnose tuberculosis. As residents represent the future providers who will be evaluating patients with possible tuberculosis, such deficiencies must be addressed