University of Missouri

About: University of Missouri is a education organization based out in Columbia, Missouri, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 41427 authors who have published 83598 publications receiving 2911437 citations. The organization is also known as: Mizzou & Missouri-Columbia.

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

Abstract: In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex.

Abstract: The bZIP transcription factor Nrf2 controls a genetic program that protects cells from oxidative damage and maintains cellular redox homeostasis. Keap1, a BTB-Kelch protein, is the major upstream regulator of Nrf2 and controls both the subcellular localization and steady-state levels of Nrf2. In this report, we demonstrate that Keap1 functions as a substrate adaptor protein for a Cul3-dependent E3 ubiquitin ligase complex. Keap1 assembles into a functional E3 ubiquitin ligase complex with Cul3 and Rbx1 that targets multiple lysine residues located in the N-terminal Neh2 domain of Nrf2 for ubiquitin conjugation both in vivo and in vitro. Keap1-dependent ubiquitination of Nrf2 is inhibited following exposure of cells to quinone-induced oxidative stress and sulforaphane, a cancer-preventive isothiocyanate. A mutant Keap1 protein containing a single cysteine-to-serine substitution at residue 151 within the BTB domain of Keap1 is markedly resistant to inhibition by either quinone-induced oxidative stress or sulforaphane. Inhibition of Keap1-dependent ubiquitination of Nrf2 correlates with decreased association of Keap1 with Cul3. Neither quinone-induced oxidative stress nor sulforaphane disrupts association between Keap1 and Nrf2. Our results suggest that the ability of Keap1 to assemble into a functional E3 ubiquitin ligase complex is the critical determinant that controls steady-state levels of Nrf2 in response to cancer-preventive compounds and oxidative stress.

What do we know about audit quality

Abstract: This paper reviews empirical research over the past 25 years, mainly from the United States, in order to assess what we currently know about audit quality with respect to publicly listed companies. The evidence indicates that outright audit failure rates are infrequent, far less than 1% annually, and audit fees are quite small, less than 0.1% of aggregate client sales. This suggests there may be an acceptable level of audit quality at a relatively low cost. There is also evidence of voluntary differential audit quality (above the legal minimum) along a number of dimensions such as firm size, industry specialization, office characteristics, and cross-country differences in legal systems and auditor liability exposure. The evidence is very positive although there is some indication that audit quality may have declined in the 1990s, in which case there could be merit in recent reforms such as the Sarbanes-Oxley Act of 2002 in the US. However, we do not know from research the optimal level of audit quality and therefore whether we currently have ‘too little’ or ‘too much’ auditing? Despite this lacuna we are entering an era of more mandated auditing in response to high-profile corporate governance failures including the Enron–Andersen affair. Finally, while recent reforms have scaled back the scope of non-audit services due to independence concerns, a case can be made that audit quality will always be somewhat suspect if other services are provided that are perceived to potentially compromise the auditor's objectivity and skepticism. For this reason public confidence in audit quality may be increased by proscribing all non-audit services for audit clients. Recommendations are also proposed with respect to legal liability reform and changes in partner compensation arrangements.

Roles of nonequilibrium conduction electrons on the magnetization dynamics of ferromagnets.

Abstract: The mutual dependence of spin-dependent conduction and magnetization dynamics of ferromagnets provides the key mechanisms in various spin-dependent phenomena. We compute the response of the conduction electron spins in a spatial and time varying magnetization M(r,t) in the time-dependent semiclassical transport theory. We show that the induced nonequilibrium conduction spin density in turn generates four spin torques acting on the magnetization-with each torque playing a different role in magnetization dynamics. By comparing with recent theoretical models, we find that one of these torques which has not been previously identified is crucial to consistently interpreting experimental data on domain wall motion.

Tests of Glycemia in Diabetes

Abstract: Monitoring of glycemic status, as performed by patients and health care providers, is considered a cornerstone of diabetes care. Results of monitoring are used to assess the efficacy of therapy and to make adjustments in diet, exercise, and medications in order to achieve the best possible blood glucose control. The purpose of this review is to summarize current knowledge about the tests used most widely in monitoring the glycemic status of people with diabetes. The review addresses both patient- and physician/laboratory-based testing, and it includes tests of urine glucose and ketones and tests of blood glucose and glycated proteins (hemoglobin and serum proteins). The major emphasis is on the advantages and limitations of each test for routine clinical practice. Use of these tests for diabetes screening and diagnosis will not be addressed in this review. Since this review was first published in 1995, there have been many advances in the field, most notably standardization of glycated hemoglobin testing and new approaches to self-monitoring of blood glucose (SMBG), including minimally invasive continuous glucose monitoring over hours to days at a time. These and other advances are presented in detail in a recent report that was prepared by the National Academy of Clinical Biochemistry (NACB) and published as an American Diabetes Association (ADA) position statement (1). This review will attempt to complement, rather than duplicate, the material in the NACB report. If there was an ideal method of monitoring glycemic status, it might be a small noninvasive device, perhaps similar to a wristwatch that people with diabetes could wear to continuously monitor their blood glucose level. The device would warn of impending hypoglycemia. It also would store blood glucose data and perform a variety of calculations such as hourly, daily, weekly, or monthly blood glucose averages. Unfortunately, such a monitoring device is …