Indiana University

About: Indiana University is a education organization based out in Bloomington, Indiana, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 64480 authors who have published 150058 publications receiving 6392902 citations. The organization is also known as: Indiana University system & indiana.edu.

Guidelines for the use and interpretation of assays for monitoring autophagy

Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.

Critical Values for Cointegration Tests in Heterogeneous Panels with Multiple Regressors

Abstract: I. INTRODUCTION In this paper we describe a method for testing the null of no cointegration in dynamic panels with multiple regressors and compute approximate critical values for these tests. Methods for non-stationary panels, including panel unit root and panel cointegration tests, have been gaining increased acceptance in recent empirical research. To date, however, tests for the null of no cointegration in heterogeneous panels based on Pedroni (1995, 1997a) have been limited to simple bivariate examples, in large part due to the lack of critical values available for more complex multivariate regressions. The purpose of this paper is to fill this gap by describing a method to implement tests for the null of no cointegration for the case with multiple regressors and to provide appropriate critical values for these cases. The tests allow for considerable heterogeneity among individual members of the panel, including heterogeneity in both the long-run cointegrating vectors as well as heterogeneity in the dynamics associated with short-run deviations from these cointegrating vectors.

Comprehensive molecular profiling of lung adenocarcinoma: The cancer genome atlas research network

Abstract: Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis.

Criteria for assessing the trustworthiness of naturalistic inquiries

Abstract: This is the ninth ERIC/ECTJ Annual Review Paper, preparation of which was supported by the ERIC (Educational Resources Information Center) Clearinghouse on Information Resources, Syracuse University, Syracuse, New York The material in this article was prepared pursuant to a contract with the National Institute of Education, US Department of Education Contractors undertaking such projects under government sponsorship are encouraged to express freely their judgment in professional and technical matters Points of view or opinions do not necessarily represent the official view or opinion of NIE The author is grateful to David Clark, Larry Havlicek, Robert Heinich, John McLaughlin, Cecil Miskel, and Robert Wolf for their careful critique of an earlier version of 1his paper, and to his wife, Yvonna Lincoln, from whose joint work with the author in other contexts many of the ideas expressed in this paper emanated

Mapping the Structural Core of Human Cerebral Cortex

Abstract: Structurally segregated and functionally specialized regions of the human cerebral cortex are interconnected by a dense network of cortico-cortical axonal pathways. By using diffusion spectrum imaging, we noninvasively mapped these pathways within and across cortical hemispheres in individual human participants. An analysis of the resulting large-scale structural brain networks reveals a structural core within posterior medial and parietal cerebral cortex, as well as several distinct temporal and frontal modules. Brain regions within the structural core share high degree, strength, and betweenness centrality, and they constitute connector hubs that link all major structural modules. The structural core contains brain regions that form the posterior components of the human default network. Looking both within and outside of core regions, we observed a substantial correspondence between structural connectivity and resting-state functional connectivity measured in the same participants. The spatial and topological centrality of the core within cortex suggests an important role in functional integration.