Celeste J. Brown

Bio: Celeste J. Brown is an academic researcher from University of Idaho. The author has contributed to research in topics: Plasmid & Gene. The author has an hindex of 42, co-authored 93 publications receiving 13322 citations. Previous affiliations of Celeste J. Brown include Indiana University – Purdue University Indianapolis & Indiana University.

Sequence complexity of disordered protein.

Abstract: Intrinsic disorder refers to segments or to whole proteins that fail to self-fold into fixed 3D structure, with such disorder sometimes existing in the native state. Here we report data on the relationships among intrinsic disorder, sequence complexity as measured by Shannon's entropy, and amino acid composition. Intrinsic disorder identified in protein crystal structures, and by nuclear magnetic resonance, circular dichroism, and prediction from amino acid sequence, all exhibit similar complexity distributions that are shifted to lower values compared to, but significantly overlapping with, the distribution for ordered proteins. Compared to sequences from ordered proteins, these variously characterized intrinsically disordered segments and proteins, and also a collection of low-complexity sequences, typically have obviously higher levels of protein-specific subsets of the following amino acids: R, K, E, P, and S, and lower levels of subsets of the following: C, W, Y, I, and V. The Swiss Protein database of sequences exhibits significantly higher amounts of both low-complexity and predicted-to-be-disordered segments as compared to a non-redundant set of sequences from the Protein Data Bank, providing additional data that nature is richer in disordered and low-complexity segments compared to the commonness of these features in the set of structurally characterized proteins.

The importance of intrinsic disorder for protein phosphorylation

Abstract: Reversible protein phosphorylation provides a major regulatory mechanism in eukaryotic cells. Due to the high variability of amino acid residues flanking a relatively limited number of experimentally identified phosphorylation sites, reliable prediction of such sites still remains an important issue. Here we report the development of a new web-based tool for the prediction of protein phosphorylation sites, DISPHOS (DISorder-enhanced PHOSphorylation predictor, http://www.ist.temple. edu/DISPHOS). We observed that amino acid compositions, sequence complexity, hydrophobicity, charge and other sequence attributes of regions adjacent to phosphorylation sites are very similar to those of intrinsically disordered protein regions. Thus, DISPHOS uses position-specific amino acid frequencies and disorder information to improve the discrimination between phosphorylation and non-phosphorylation sites. Based on the estimates of phosphorylation rates in various protein categories, the outputs of DISPHOS are adjusted in order to reduce the total number of misclassified residues. When tested on an equal number of phosphorylated and non-phosphorylated residues, the accuracy of DISPHOS reaches 76% for serine, 81% for threonine and 83% for tyrosine. The significant enrichment in disorder-promoting residues surrounding phosphorylation sites together with the results obtained by applying DISPHOS to various protein functional classes and proteomes, provide strong support for the hypothesis that protein phosphorylation predominantly occurs within intrinsically disordered protein regions.

Intrinsic protein disorder in complete genomes.

Abstract: Intrinsic protein disorder refers to segments or to whole proteins that fail to fold completely on their own. Here we predicted disorder on protein sequences from 34 genomes, including 22 bacteria, 7 archaea, and 5 eucaryotes. Predicted disordered segments > or = 50, > or = 40, and > or = 30 in length were determined as well as proteins estimated to be wholly disordered. The five eucaryotes were separated from bacteria and archaea by having the highest percentages of sequences predicted to have disordered segments > or = 50 in length: from 25% for Plasmodium to 41% for Drosophila. Estimates of wholly disordered proteins in the bacteria ranged from 1% to 8%, averaging to 3 +/- 2%, estimates in various archaea ranged from 2 to 11%, plus an apparently anomalous 18%, averaging to 7 +/- 5% that drops to 5 +/- 3% if the high value is discarded. Estimates in the 5 eucarya ranged from 3 to 17%. The putative wholly disordered proteins were often ribosomal proteins, but in addition about equal numbers were of known and unknown function. Overall, intrinsic disorder appears to be a common, with eucaryotes perhaps having a higher percentage of native disorder than archaea or bacteria.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling

Abstract: Motivation: Homology models of proteins are of great interest for planning and analysing biological experiments when no experimental three-dimensional structures are available. Building homology models requires specialized programs and up-to-date sequence and structural databases. Integrating all required tools, programs and databases into a single web-based workspace facilitates access to homology modelling from a computer with web connection without the need of downloading and installing large program packages and databases. Results: SWISS-MODEL workspace is a web-based integrated service dedicated to protein structure homology modelling. It assists and guides the user in building protein homology models at different levels of complexity. A personal working environment is provided for each user where several modelling projects can be carried out in parallel. Protein sequence and structure databases necessary for modelling are accessible from the workspace and are updated in regular intervals. Tools for template selection, model building and structure quality evaluation can be invoked from within the workspace. Workflow and usage of the workspace are illustrated by modelling human Cyclin A1 and human Transmembrane Protease 3. Availability: The SWISS-MODEL workspace can be accessed freely at http://swissmodel.expasy.org/workspace/ Contact: Torsten.Schwede@unibas.ch Supplementary information: Supplementary data are available at Bioinformatics online.

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

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. For example, 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 versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase 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. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. 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. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. 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 assays, we hope to encourage technical innovation in the field.

“Bioinformatics” 특집을 내면서

Abstract: BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

Estimation and Inference in Econometrics

Abstract: Offering a unifying theoretical perspective not readily available in any other text, this innovative guide to econometrics uses simple geometrical arguments to develop students' intuitive understanding of basic and advanced topics, emphasizing throughout the practical applications of modern theory and nonlinear techniques of estimation. One theme of the text is the use of artificial regressions for estimation, reference, and specification testing of nonlinear models, including diagnostic tests for parameter constancy, serial correlation, heteroscedasticity, and other types of mis-specification. Explaining how estimates can be obtained and tests can be carried out, the authors go beyond a mere algebraic description to one that can be easily translated into the commands of a standard econometric software package. Covering an unprecedented range of problems with a consistent emphasis on those that arise in applied work, this accessible and coherent guide to the most vital topics in econometrics today is indispensable for advanced students of econometrics and students of statistics interested in regression and related topics. It will also suit practising econometricians who want to update their skills. Flexibly designed to accommodate a variety of course levels, it offers both complete coverage of the basic material and separate chapters on areas of specialized interest.