bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patika: an integrated visual environment
for collaborative construction and analysis of cellular
pathways
Authors: Demir E. , Babur O. , Dogrusoz U. , Gursoy A. , Nisanci G. , Cetin-Atalay R. , Ozturk M. 
Published: July 2002

Abstract
Motivation: Availability of the sequences of entire genomes shifts the scientific curiosity towards the identification of function of the genomes in large scale as in genome studies. In the near future, data produced about cellular processes at molecular level will accumulate with an accelerating rate as a result of proteomics studies. In this regard, it is essential to develop tools for storing, integrating, accessing, and analyzing this data effectively.
Results: We define an ontology for a comprehensive representation of cellular events. The ontology presented here enables integration of fragmented or incomplete pathway information and supports manipulation and incorporation of the stored data, as well as multiple levels of abstraction. Based on this ontology, we present the architecture of an integrated environment named Patika (Pathway Analysis Tool for Integration and Knowledge Acquisition). Patika is composed of a server-side, scalable, object-oriented database and client-side editors to provide an integrated, multi-user environment for visualizing and manipulating network of cellular events. This tool features automated pathway layout, functional computation support, advanced querying and a user-friendly graphical interface.
We expect that Patika will be a valuable tool for rapid knowledge acquisition, microarray generated large-scale data interpretation, disease gene identification, and drug development.
Availability: A prototype of Patika is available upon request from the authors.
Contact: patika@cs.bilkent.edu.tr
* To whom correspondence should be addressed.
Interactive Exploration of Microarray Gene Expression Patterns in a Reduced Dimensional Space
Authors: Misra Jatin , Schmitt William , Hwang Daehee , Hsiao Li-Li , Gullans Steve , Stephanopoulos George , Stephanopoulos Gregory 
Published: July 2002

The very high dimensional space of gene expression measurements obtained by DNA microarrays impedes the detection of underlying patterns in gene expression data and the identification of discriminatory genes. In this paper we show the use of projection methods such as principal components analysis (PCA) to obtain a direct link between patterns in the genes and patterns in samples. This feature is useful in the initial interactive pattern exploration of gene expression data and data-driven learning of the nature and types of samples. Using oligonucleotide microarray measurements of 40 samples from different normal human tissues, we show that distinct patterns are obtained when the genes are projected on a two-dimensional plane spanned by the loadings of the two major principal components. These patterns define the particular genes associated with a sample class (i.e., tissue). When used separately from the other genes, these class-specific (i.e., tissue-specific) genes in turn define distinct tissue patterns in the projection space spanned by the scores of the two major principal components. In this study, PCA projection facilitated discriminatory gene selection for different tissues and identified tissue-specific gene expression signatures for liver, skeletal muscle, and brain samples. Furthermore, it allowed the classification of nine new samples belonging to these three types using the linear combination of the expression levels of the tissue-specific genes determined from the first set of samples. The application of the technique to other published data sets is also discussed.[Online supplementary material available atwww.genome.org.]
Transcript Profiling of Functionally Related Groups of Genes During Conditional Differentiation of a Mammalian Cochlear Hair Cell Line
Authors: Rivolta Marcelo N. , Halsall Antony , Johnson Claire M. , Tones Michael A. , Holley Matthew C. 
Published: July 2002

We have used Affymetrix high-density gene arrays to generate a temporal profile of gene expression during differentiation of UB/OC-1, a conditionally immortal cell line derived from the mouse cochlea. Gene expression was assessed daily for 14 days under differentiating conditions. The experiment was replicated in two separate populations of cells. Profiles for selected genes were correlated with those obtained by RT-PCR, TaqMan analysis, immunoblotting, and immunofluorescence. The results suggest that UB/OC-1 is derived from a population of nonsensory epithelial cells in the greater epithelial ridge that have the potential to differentiate into a hair-cell-like phenotype, without the intervention of Math1. Elements of the Notch signaling cascade were identified, including the receptorNotch3, with a transient up-regulation that suggests a role in hair cell differentiation. Several genes showed a profile similar toNotch3, including the transcriptional co-repressorGroucho1. UB/OC-1 also expressed Me1, a putative partner of Math1 that may confer competence to differentiate into hair cells. Cluster analysis revealed expression profiles for neural guidance genes associated with Gata3. The temporal dimension of this analysis provides a powerful tool to study genetic mechanisms that underlie the conversion of nonsensory epithelial cells into hair cells.[The entire data set published in this paper has been deposited in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus Database (http://www.ncbi.nlm.nih.gov/geo/) under the series accession no. GSE36 and sample numbers contained therein. Supplementary material is available online at http://www.genome.org. The following individuals kindly provided reagents, samples or unpublished information as indicated in the paper: T. Hasson, C. Petit, and P. Matsudaira]
Profiling Patterned Transcripts in Drosophila Embryos
Authors: Simin Karl , Scuderi Anne , Reamey James , Dunn Diane , Weiss Robert , Metherall James E. , Letsou Anthea 
Published: July 2002

Here we describe a high-throughput screen to isolate transcripts with spatially restricted patterns of expression in early embryos. Our approach utilizes robotic automation for rapid analysis of sequence-selected cDNAs in a whole-mount in situ hybridization assay. We determined the spatial distribution of a random collection of 778 different genes from an embryonic cDNA library and show that a significant fraction of these exhibit patterned profiles of expression. In addition, gene ontology studies revealed groups of gene products exhibiting shared expression patterns, providing new insights into the largely overlooked effector molecules that function in development. As described in this paper, automated hybridization to whole-mount embryos in situ proved to be straightforward and provided us with a very powerful method for the global survey of gene expression in early embryos. From the perspective of biological significance, our finding that many spatially restricted transcripts correspond to loci encoding novel transcripts that have not been previously identified in nearly saturating genetic screens for maternal effect and zygotic lethals is particularly notable.[Supplementary material available online at http://www.genome.org. The following individuals kindly provided reagents, samples, or unpublished information as indicated in the paper: N. Brown]
Heat Stress- and Heat Shock Transcription Factor-Dependent Expression and Activity of Ascorbate Peroxidase in Arabidopsis
Authors: Panchuk Irina I. , Volkov Roman A. , Schöffl Friedrich 
Published: July 2002

Abstract
To find evidence for a connection between heat stress response, oxidative stress, and common stress tolerance, we studied the effects of elevated growth temperatures and heat stress on the activity and expression of ascorbate peroxidase (APX). We compared wild-type Arabidopsis with transgenic plants overexpressing heat shock transcription factor 3 (HSF3), which synthesize heat shock proteins and are improved in basal thermotolerance. Following heat stress, APX activity was positively affected in transgenic plants and correlated with a new thermostable isoform, APXS. This enzyme was present in addition to thermolabile cytosolic APX1, the prevalent isoform in unstressed cells. In HSF3-transgenic plants, APXS activity was detectable at normal temperature and persisted after severe heat stress at 44°C. In nontransgenic plants, APXS was undetectable at normal temperature, but could be induced by moderate heat stress. The mRNA expression profiles of known and three new Apx genes were determined using real-time PCR. Apx1 and Apx2 genes encoding cytosolic APX were heat stress and HSF dependently expressed, but only the representations of Apx2 mRNA met the criteria that suggest identity between APXS and APX2: not expressed at normal temperature in wild type, strong induction by heat stress, and HSF3-dependent expression in transgenic plants. Our data suggest thatApx2 is a novel heat shock gene and that the enzymatic activity of APX2/APXS is required to compensate heat stress-dependent decline of APX1 activity in the cytosol. The functional roles of modulations of APX expression and the interdependence of heat stress and oxidative stress response and signaling mechanisms are discussed.
Regulation of Squalene Synthase, a Key Enzyme of Sterol Biosynthesis, in Tobacco
Authors: Devarenne Timothy P. , Ghosh Anirban , Chappell Joe 
Published: July 2002

AbstractSqualene synthase (SS) represents a putative branch point in the isoprenoid biosynthetic pathway capable of diverting carbon flow specifically to the biosynthesis of sterols and, hence, is considered a potential regulatory point for sterol metabolism. For example, when plant cells grown in suspension culture are challenged with fungal elicitors, suppression of sterol biosynthesis has been correlated with a reduction in SS enzyme activity. The current study sought to correlate changes in SS enzyme activity with changes in the level of the corresponding protein and mRNA. Using an SS-specific antibody, the initial suppression of SS enzyme activity in elicitor-challenged cells was not reflected by changes in the absolute level of the corresponding polypeptide, implicating a post-translational control mechanism for this enzyme activity. In comparison, the absolute level of the SS mRNA did decrease approximately 5-fold in the elicitor-treated cells, which is suggestive of decreased transcription of the SS gene. Study of SS in intact plants was also initiated by measuring the level of SS enzyme activity, the level of the corresponding protein, and the expression of SS gene promoter-reporter gene constructs in transgenic plants. SS enzyme activity, polypeptide level, and gene expression were all localized predominately to the shoot apical meristem, with much lower levels observed in leaves and roots. These later results suggest that sterol biosynthesis is localized to the apical meristems and that apical meristems may be a source of sterols for other plant tissues.
The Branched-Chain Amino Acid Transaminase Gene Family in Arabidopsis Encodes Plastid and Mitochondrial Proteins
Authors: Diebold Ruth , Schuster Joachim , Däschner Klaus , Binder Stefan 
Published: July 2002

Abstract
Branched-chain amino acid transaminases (BCATs) play a crucial role in the metabolism of leucine, isoleucine, and valine. They catalyze the last step of the synthesis and/or the initial step of the degradation of this class of amino acids. In Arabidopsis, seven putative BCAT genes are identified by their similarity to their counterparts from other organisms. We have now cloned the respective cDNA sequences of six of these genes. The deduced amino acid sequences show between 47.5% and 84.1% identity to each other and about 30% to the homologous enzymes from yeast (Saccharomyces cerevisiae) and mammals. In addition, many amino acids in crucial positions as determined by crystallographic analyses of BCATs from Escherichia coli and human (Homo sapiens) are conserved in the AtBCATs. Complementation of a yeast Δbat1/Δbat2 double knockout strain revealed that five AtBCATs can function as BCATs in vivo. Transient expression of BCAT:green fluorescent protein fusion proteins in tobacco (Nicotiana tabacum) protoplasts shows that three isoenzymes are imported into chloroplasts (AtBCAT-2, -3, and -5), whereas a single enzyme is directed into mitochondria (AtBCAT-1).
Salt Induction of Fatty Acid Elongase and Membrane Lipid Modifications in the Extreme Halotolerant Alga Dunaliella salina
Authors: Azachi Malkit , Sadka Avi , Fisher Morly , Goldshlag Paulina , Gokhman Irena , Zamir Ada 
Published: July 2002

Abstract
In studies of the outstanding salt tolerance of the unicellular green alga Dunaliella salina, we isolated a cDNA for a salt-inducible mRNA encoding a protein homologous to plant β-ketoacyl-coenzyme A (CoA) synthases (Kcs). These microsomal enzymes catalyze the condensation of malonyl-CoA with acyl-CoA, the first and rate-limiting step in fatty acid elongation. Kcs activity, localized to a D. salina microsomal fraction, increased in cells transferred from 0.5 to 3.5 m NaCl, as did the level of thekcs mRNA. The function of the kcsgene product was directly demonstrated by the condensing activity exhibited by Escherichia coli cells expressing thekcs cDNA. The effect of salinity on kcsexpression in D. salina suggested the possibility that salt adaptation entailed modifications in the fatty acid composition of algal membranes. Lipid analyses indicated that microsomes, but not plasma membranes or thylakoids, from cells grown in 3.5 mNaCl contained a considerably higher ratio of C18 (mostly unsaturated) to C16 (mostly saturated) fatty acids compared with cells grown in 0.5m salt. Thus, the salt-inducible Kcs, jointly with fatty acid desaturases, may play a role in adapting intracellular membrane compartments to function in the high internal glycerol concentrations balancing the external osmotic pressure.
Differential Accumulation of Dimethylallyl Diphosphate in Leaves and Needles of Isoprene- and Methylbutenol-Emitting and Nonemitting Species
Authors: Rosenstiel Todd N. , Fisher Alison J. , Fall Ray , Monson Russell K. 
Published: July 2002

Abstract
The biosynthesis and emission of volatile plant terpenoids, such as isoprene and methylbutenol (MBO), depend on the chloroplastic production of dimethylallyl diphosphate (DMAPP). To date, it has been difficult to study the relationship of cellular DMAPP levels to emission of these volatiles because of the lack of a sensitive assay for DMAPP in plant tissues. Using a recent DMAPP assay developed in our laboratories, we report that species with the highest potential for isoprene and MBO production also exhibit elevated light-dependent DMAPP production, ranging from 110% to 1,063%. Even species that do not produce significant amounts of volatile terpenoids, however, exhibit some potential for light-dependent production of DMAPP. We used a nonaqueous fractionation technique to determine the intracellular distribution of DMAPP in isoprene-emitting cottonwood (Populus deltoides) leaves; approximately 65% to 70% of the DMAPP recovered at midday occurred in the chloroplasts, indicating that most of the light-dependent production of DMAPP was chloroplastic in origin. The midday concentration of chloroplastic DMAPP in cottonwood leaves is estimated to be 0.13 to 3.0 mm, which is consistent with the relatively high K ms that have been reported for isoprene synthases (0.5–8 mm). The results provide support for the hypothesis that the light dependence of isoprene and MBO emissions is in part due to controls over DMAPP production.
NPSN11 Is a Cell Plate-Associated SNARE Protein That Interacts with the Syntaxin KNOLLE
Authors: Zheng Haiyan , Bednarek Sebastian Y. , Sanderfoot Anton A. , Alonso Jose , Ecker Joseph R. , Raikhel Natasha V. 
Published: July 2002

Abstract
SNAREs are important components of the vesicle trafficking machinery in eukaryotic cells. In plants, SNAREs have been found to play a variety of roles in the development and physiology of the whole organism. Here, we describe the identification and characterization of a novel plant-specific SNARE, NPSN11, a member of a closely related small gene family in Arabidopsis. NSPN11 is highly expressed in actively dividing cells. In a subcellular fractionation experiment, NSPN11 cofractionates with the cytokinesis-specific syntaxin, KNOLLE, which is required for the formation of the cell plate. By immunofluorescence microscopy, NSPN11 was localized to the cell plate in dividing cells. Consistent with the localization studies, NSPN11 was found to interact with KNOLLE. Our results suggest that NPSN11 is another component of the membrane trafficking and fusion machinery involved in cell plate formation.
Combinatorial Interaction of Cis Elements Specifies the Expression of the Arabidopsis AtHsp90-1Gene
Authors: Haralampidis Kosmas , Milioni Dimitra , Rigas Stamatis , Hatzopoulos Polydefkis 
Published: July 2002

Abstract
The promoter region of the ArabidopsisAtHsp90-1 gene is congested with heat shock elements and stress response elements, as well as with other potential transcriptional binding sites (activating protein 1, CCAAT/enhancer-binding protein element, and metal regulatory element). To determine how the expression of this bona fideAtHsp90-1 gene is regulated, a comprehensive quantitative and qualitative promoter deletion analysis was conducted under various environmental conditions and during development. The promoter induces gene expression at high levels after heat shock and arsenite treatment. However, our results show that the two stress responses may involve common but not necessarily the same regulatory elements. Whereas for heat induction, heat shock elements and stress response elements act cooperatively to promote high levels of gene expression, arsenite induction seems to require the involvement of activating protein 1 regulatory sequences. In stressed transgenic plants harboring the full-length promoter, β-glucuronidase activity was prominent in all tissues. Nevertheless, progressive deletion of the promoter decreases the level of expression under heat shock and restricts it predominantly in the two meristems of the plant. In contrast, under arsenite induction, proximal sequences induceAtHsp90-1 gene expression only in the shoot meristem. Distally located elements negatively regulate AtHsp90-1gene expression under unstressed conditions, whereas flower-specific regulated expression in mature pollen grains suggests the prominent role of the AtHsp90-1 in pollen development. The results show that the regulation of developmental expression, suppression, or stress induction is mainly due to combinatorial contribution of the cis elements in the promoter region of the AtHsp90-1gene.
Role of a Heterotrimeric G Protein in Regulation of Arabidopsis Seed Germination
Authors: Ullah Hemayet , Chen Jin-Gui , Wang Shucai , Jones Alan M. 
Published: July 2002

AbstractSeed germination is regulated by many signals. We investigated the possible involvement of a heterotrimeric G protein complex in this signal regulation. Seeds that carry a protein null mutation in the gene encoding the alpha subunit of the G protein in Arabidopsis (GPA1) are 100-fold less responsive to gibberellic acid (GA), have increased sensitivity to high levels of Glc, and have a near-wild-type germination response to abscisic acid and ethylene, indicating that GPA1 does not directly couple these signals in germination control. Seeds ectopically expressingGPA1 are at least a million-fold more responsive to GA, yet still require GA for germination. We conclude that the GPA1 indirectly operates on the GA pathway to control germination by potentiation. We propose that this potentiation is directly mediated by brassinosteroids (BR) because the BR response and synthesis mutants,bri1-5 and det2-1, respectively, share the same GA sensitivity as gpa1 seeds. Furthermore,gpa1 seeds are completely insensitive to brassinolide rescue of germination when the level of GA in seeds is reduced. A lack of BR responsiveness is also apparent in gpa1 roots and hypocotyls suggesting that BR signal transduction is likely coupled by a heterotrimeric G protein at various points in plant development.
Endogenous and Silencing-Associated Small RNAs in Plants[W]
Authors: Llave Cesar , Kasschau Kristin D. , Rector Maggie A. , Carrington James C. 
Published: July 2002

AbstractA large set of endogenous small RNAs of predominantly 21 to 24 nucleotides was identified in Arabidopsis. These small RNAs resembled micro-RNAs from animals and were similar in size to small interfering RNAs that accumulated during RNA silencing triggered by multiple types of inducers. Among the 125 sequences identified, the vast majority (90%) arose from intergenic regions, although small RNAs corresponding to predicted protein-coding genes, transposon-like sequences, and a structural RNA gene also were identified. Evidence consistent with the derivation of small RNAs of both polarities, and from highly base-paired precursors, was obtained through the identification and analysis of clusters of small RNA loci. The accumulation of specific small RNAs was regulated developmentally. We propose that Arabidopsis small RNAs participate in a wide range of post-transcriptional and epigenetic events.
The fibril_one on‐line database: Mutations, experimental conditions, and trends associated with amyloid fibril formation
Authors: Siepen Jennifer A. , Westhead David R. 
Published: July 2002

AbstractThe association of amyloid fibril formation with a number of important diseases, and the extensive study of this process in vitro, has resulted in a large literature containing a vast amount of information about the fibril formation process. This includes mutations and experimental conditions that promote or protect against fibril formation. A database (fibril_one) was designed to hold information relating to the formation of fibrils. It was populated by extensive searches of the literature and other databases. A powerful World Wide Web query interface to the database was developed, enabling a simple and effective method to view amyloidogenic mutations associated with specific proteins. The Web interface was used to identify trends in the data. This revealed that mutations promoting fibril formation through altered folding tend to be associated with destabilization of the native fold. In particular, tendancies of mutations to disrupt the native secondary structure and packing in the hydrophobic core were discovered to be significant. Query access to the database is available freely on the World Wide Web at http://www.bioinformatics.leeds.ac.uk/group/online/fibril_one.
Correlation of protein functional properties in the crystal and in solution: The case study of T‐state hemoglobin
Authors: Noble Robert W. , Kwiatkowski Laura D. , Hui Hilda L. , Bruno Stefano , Bettati Stefano , Mozzarelli Andrea 
Published: July 2002

AbstractThe relevance of three‐dimensional structures of proteins, determined by X‐ray crystallography, is an important issue that is becoming even more critical in light of the Structural Genomics Initiative. As a case study, a detailed comparison of functional properties of the T quaternary states of genetically or chemically modified human hemoglobins (Hbs) in solution and in the crystal was performed. Oxygen affinities of Hbs in crystals correlate with the rate constants of their initial combination with carbon monoxide (CO) in solution, indicating that changes in ligand affinity caused by the modifications are similarly observed in both physical states.