bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dexamethasone‐induced and estradiol‐induced CREB activation and annexin 1 expression in CCRF‐CEM lymphoblastic cells: evidence for the involvement of cAMP and p38 MAPK
Authors: Castro-caldas M. , Mendes A. F. , Duarte C. B. , Lopes M. C. F. 
Published: December 2003

Aims: Annexin 1 (ANXA1), a member of the annexin family of calcium‐binding and phospholipid‐binding proteins, is a key mediator of the anti‐inflammatory actions of steroid hormones. We have previously demonstrated that, in the human lymphoblastic CCRF‐CEM cell line, both the synthetic glucocorticoid hormone, dexamethasone (Dex), and the estrogen hormone, 17β‐estradiol (E2β), induce the synthesis of ANXA1, by a mechanism independent of the activation of their nuclear receptors. Recently, it was reported that the gene coding for ANXA1 contains a cAMP‐responsive element (CRE). In this work, we investigated whether Dex and E2β were able to induce the activation of CRE binding proteins (CREB) in the CCRF‐CEM cells. Moreover, we studied the intracellular signalling pathways involved in CREB activation and ANXA1 synthesis in response to Dex and E2β; namely, the role of cAMP and the p38 mitogen‐activated protein kinase (MAPK).Results: The results show that Dex and E2β were as effective as the cAMP analogue, dBcAMP, in inducing CREB activation. On the other hand, dBcAMP induced ANXA1 synthesis as effectively as these steroid hormones. Furthermore, the cAMP antagonist, Rp‐8‐Br‐cAMPS, and the specific p38 MAPK inhibitor, SB203580, effectively prevented Dex‐induced, E2β‐induced and dBcAMP‐induced CREB activation and ANXA1 synthesis.Conclusions: Taken together, our results suggest that, in CCRF‐CEM cells, Dex‐induced and E2β‐induced ANXA1 expression requires the activation of the transcription factor CREB, which in turn seems to be mediated by cAMP and the p38 MAPK. These findings also suggest that, besides the nuclear steroid hormone receptors, other transcription factors, namely CREB, may play important roles in mediating the anti‐inflammatory actions of glucocorticoids and oestrogen hormones.
Levels of serum IL‐1β, IL‐2, IL‐8 and tumor necrosis factor‐α in patients with unstable angina pectoris
Authors: Ozeren Ali , Aydin Mustafa , Tokac Mehmet , Demircan Nejat , Unalacak Murat , Gurel Ahmet , Yazici Mehmet 
Published: December 2003

Objectives: Inflammation is the most important mechanism of plaque disruption playing an essential role in acute coronary syndromes. It is controversial whether the inflammatory mediators are the cause or the result in the development of plaque rupture. Stimulation of interleukins increases adhesion molecules, fibrinogen and plasminogen activator inhibitors, which cause the activation of inflammation and thrombosis. However, the importance of interleukins in acute coronary syndromes has not been clearly defined. We did not find any article concerning relations between the levels of serum interleukin (IL)‐1β, IL‐2, IL ‐8 and tumor necrosis factor (TNF)‐α in patients with unstable angina pectoris (UAP). So the aim of this study was to determine the levels of serum IL‐1β, IL‐2, IL‐8 and TNF‐α during the early stage of UAP.Methods and results: Thirty‐seven patients with UAP (12 females and 25 males; mean age, 57.5±9.7 years) within 6 h of admission and 20 healthy volunteers (eight females and 12 males; mean age, 51.3±6.3 years) were included in the study. IL‐1β, IL‐2, IL‐8 and TNF‐α levels were measured using the enzyme‐linked immunosorbent assay method. Patients with acute or chronic inflammation, renal failure or chronic heart failure were excluded from the study. The age, gender and risk factors of the study and control groups were similar. The levels of IL‐1β, IL‐8 and TNF‐α were significantly increased (p < 0.0001, p < 0.001 and p < 0.016, respectively) in patients with UAP. There was no difference of IL‐2 levels between the UAP group and controls.Conclusion: We detected high levels of IL‐1β, IL‐8 and TNF‐α in patients with UAP during early phase. We suggest that proinflammatory cytokines (e.g. IL‐1β, IL‐8, TNF‐α) may play an important role in the development of atherosclerosis and its complications.
Radiation‐Induced Leiomyosarcoma: Does Antimetabolite ChemotherapyContribute? A Report of Three Cases
Authors: Brockstein Bruce , Mundt Arno , Haraf Daniel J. , Ferguson Mark , Montag Anthony 
Published: December 2003

Purpose: Radiation therapy in low and high doses is known to be associated with the occurrence of late secondary sarcomas.
The addition of chemotherapy has not been clearly demonstrated as a contributing factor. We describe three patients with
radiation‐associated leiomyosarcoma who had also received antimetabolite chemotherapy.Methods: Three cases of leiomyosarcoma occurring 9–27 years after radiation and antimetabolite chemotherapy are
presented, along with histopathological details. A Medline search was used to assess prior reports of leiomyosarcoma after
radiation.Results: These three cases appear to be the first reported in which leiomyosarcoma followed therapy with radiation and
antimetabolites.Discussion: With the increasing use of antimetabolite therapy combined with radiation, there is the potential for more
occurrences of leiomyosarcoma or other post‐treatment sarcomas.
Mitochondrial Nitric‐oxide Synthase: Role in Pathophysiology
Authors: Haynes Virginia , Elfering Sarah , Squires Rachel , Traaseth Nathaniel , Solien Joseph , Ettl Adam , Giulivi Cecilia 
Published: December 2003

AbstractThe biochemistry of the mitochondrial production of nitric oxide is reviewed to gain insight into the basic role of this radical in mitochondrial and cellular oxidative metabolism. The mitochondrial production of nitric oxide is catalyzed by a nitric‐oxide synthase (mtNOS). This enzyme has the same cofactor and substrate requirements as other constitutive nitric‐oxide synthases. Its occurrence was demonstrated in various mitochondrial preparations from different organs and species using diverse approaches (oxidation of oxymyoglobin, electron paramagnetic resonance in conjunction with spin trap, radiolabeled L‐arginine, immunohistochemistry, nitric‐oxide electrode). MtNOS has been identified as the alpha isoform of nNOS, acylated at a Thr or Ser residue, and phosphorylated at the C‐terminal end. Endogenous nitric oxide reversibly inhibits oxygen consumption and ATP synthesis by competitive inhibition of cytochrome oxidase. Nitric oxide is the first molecule that fulfills the requirement for a cytochrome oxidase activity modulator: it is a competitive inhibitor, produced endogenously at a fair rate near the target site, at concentrations high enough to exhibit an inhibitory effect on cytochrome oxidase. The role of the mitochondrial nitric oxide production is discussed in terms of the physiological (modulating oxygen gradients into tissues) and pathological (abrogation of oxygen gradient modification, apoptosis, protein nitrative/oxidative stress) implications. IUBMB Life, 55: 599‐603, 2003
Genetic Aberrations in Chernobyl‐Related Thyroid Cancers: Implications for Possible Future Nuclear Accidents or Nuclear Attacks
Authors: Ermak Gennady , Figge James J. , Kartel Nikolai A. , Davies Kelvin JA 
Published: December 2003

AbstractCases of thyroid cancer among children in Belarus represent a unique model system in which the cause of the cancer is known ‐ radiation. Although other sources of radiation‐induced cancers are diminishing (survivors of Hiroshima and Nagasaki, and individuals exposed to diagnostic or therapeutic radiation) fears of radiation exposure from accidents and terrorism are increasing. Our analysis of current data reveals that Chernobyl‐related cancer cases might have a specific pattern of genetic aberrations. These data strongly confirm the hypothesis that radiation‐induced cancers might arise as a result of specific gene aberrations that are distinct from those in sporadic cancers, suggesting that methods of prevention and treatment of radiation‐induced cancers might require a different approach. Understanding of the molecular mechanisms of Chernobyl‐related papillary thyroid carcinomas will help to identify mechanisms by which radiation causes aberrations and oncogenic cell transformation. Thus, in turn, it will be important in the development of new treatments or technologies to minimize the effects of radiation damage from nuclear accidents or nuclear attacks. IUBMB Life, 55: 637‐641, 2003
Control of the Nitric Oxide‐Cytochrome c Oxidase Signaling Pathway under Pathological and Physiological Conditions
Authors: Shiva Sruti , Darley‐Usmar Victor 
Published: December 2003

AbstractProminent among the mechanisms of interaction of nitric oxide (NO) with intracellular targets are the reactions with heme proteins. For example, the mechanism through which NO induces synthesis of the second messenger cyclic GMP involves the binding of NO to the heme in soluble guanylate cyclase. It has only recently been appreciated that NO binding to the binuclear oxygen binding site in cytochrome c oxidase may also serve as a signal transduction pathway. We postulate that NO is uniquely positioned to control mitochondrial respiration and in doing so regulates oxygen gradients within the cell. In this short overview the mechanisms of NO‐dependent regulation of mitochondrial function will be discussed in the context of some of the biological and physiological consequences. IUBMB Life, 55: 585‐590, 2003
Efficient filtering methods for clustering cDNAs with spliced sequence alignment
Authors: Shibuya Tetsuo , Kashima Hisashi , Konagaya Akihiko 
Published: December 2003

Abstract
Motivation: Clustering sequences of a full-length cDNA library into alternative splice form candidates is a very important problem.
Results: We developed a new efficient algorithm to cluster sequences of a full-length cDNA library into alternative splice form candidates. Current clustering algorithms for cDNAs tend to produce too many clusters containing incorrect splice form candidates. Our algorithm is based on a spliced sequence alignment algorithm that considers splice sites. The spliced sequence alignment algorithm is a variant of an ordinary dynamic programming algorithm, which requires O(nm) time for checking a pair of sequences where n and m are the lengths of the two sequences. Since the time bound is too large to perform all-pair comparison for a large set of sequences, we developed new techniques to reduce the computation time without affecting the accuracy of the output clusters. Our algorithm was applied to 21 076 mouse cDNA sequences of the FANTOM 1.10 database to examine its performance and accuracy. In these experiments, we achieved about 2–12-fold speedup against a method using only a traditional hash-based technique. Moreover, without using any information of the mouse genome sequence data or any gene data in public databases, we succeeded in listing 87–89% of all the clusters that biologists have annotated manually.
Availability: We provide a web service for cDNA clustering located at https://access.obigrid.org/ibm/cluspa/, for which registration for the OBIGrid (http://www.obigrid.org) is required.
GIS: a biomedical text-mining system for gene information discovery
Authors: Chiang Jung-Hsien , Yu Hsu-Chun , Hsu Huai-Jen 
Published: December 2003

Abstract
Summary: We present a biomedical text-mining system focused on four types of gene-related information: biological functions, associated diseases, related genes and gene–gene relations. The aim of this system is to provide researchers an easy-to-use bio-information service that will rapidly survey the rapidly burgeoning biomedical literature.
Availability: http://iir.csie.ncku.edu.tw/~yuhc/gis/
GRIL: genome rearrangement and inversion locator
Authors: Darling Aaron E. , Mau Bob , Blattner Frederick R. , Perna Nicole T. 
Published: December 2003

Abstract
Summary: GRIL is a tool to automatically identify collinear regions in a set of bacterial-size genome sequences. GRIL uses three basic steps. First, regions of high sequence identity are located. Second, some of these regions are filtered based on user-specified criteria. Finally, the remaining regions of sequence identity are used to define significant collinear regions among the sequences. By locating collinear regions of sequence, GRIL provides a basis for multiple genome alignment using current alignment systems. GRIL also provides a basis for using current inversion distance tools to infer phylogeny.
Availability: GRIL is implemented in C++ and runs on any x86-based Linux or Windows platform. It is available from http://asap.ahabs.wisc.edu/gril
Supplementary information: The GRIL web site contains a detailed description of the GRIL's algorithms, an example of applying GRIL to five genomes, and verification of the correctness of the results.
WILMA—automated annotation of protein sequences
Authors: Prlić Andreas , Domingues Francisco S. , Lackner Peter , Sippl Manfred J. 
Published: December 2003

Abstract
Summary: Large-scale annotation of sets of proteins is a frequently occurring task in association with genome sequencing projects. Here, we present an automated platform for the functional annotation of large sets of protein sequences. Various bioinformatics tools are used to achieve a comprehensive description of protein sequences and to link these results to standard Gene Ontology descriptors for molecular function, biological processes and cellular components. Access to the annotation is provided via a web-interface and database queries. These interfaces allow to formulate proteome wide queries as well as the investigation of details of individual results. WILMA annotations of the proteomes of Homo sapiens, Mus musculus, Arabidopsis thaliana and Caenorhabditis elegans are accessible at http://www.came.sbg.ac.at/wilma/
A global test for groups of genes: testing association with a clinical outcome
Authors: Goeman Jelle J. , van de Geer Sara A. , de Kort Floor , van Houwelingen Hans C. 
Published: December 2003

Abstract
Motivation: This paper presents a global test to be used for the analysis of microarray data. Using this test it can be determined whether the global expression pattern of a group of genes is significantly related to some clinical outcome of interest. Groups of genes may be any size from a single gene to all genes on the chip (e.g. known pathways, specific areas of the genome or clusters from a cluster analysis).
Result: The test allows groups of genes of different size to be compared, because the test gives one p-value for the group, not a p-value for each gene. Researchers can use the test to investigate hypotheses based on theory or past research or to mine gene ontology databases for interesting pathways. Multiple testing problems do not occur unless many groups are tested. Special attention is given to visualizations of the test result, focussing on the associations between samples and showing the impact of individual genes on the test result.
Availability: An R-package globaltest is available from http://www.bioconductor.org
BugView: a browser for comparing genomes
Authors: Leader David P. 
Published: December 2003

Abstract
Summary: BugView is a Java application for visualizing homologous genes on a pair of related genomes, and can also be used to view individual genomes. It accepts files of prokaryotic or eukaryotic genomes in GenBank format and allows users to assign homologous pairs, and make and save annotations.
Availability: http://www.gla.ac.uk/~dpl1n/BugView/
Supplementary information: http://www.gla.ac.uk/~dpl1n/BugView/BugViewManual.pdf provides a full description of the application.
HNH family subclassification leads to identification of commonality in the His‐Me endonuclease superfamily
Authors: Mehta Preeti , Katta Krishnamohan , Krishnaswamy Sankaran 
Published: December 2003

AbstractThe HNHc (SMART ID: SM00507) domain (SCOP nomenclature: HNH family) can be subclassified into at least eight subsets by iterative refinement of HMM profiles. An initial clustering of 323 proteins containing the HNHc domain helped identify the subsets. The subsets could be differentiated on the basis of the pattern of occurrence of seven defining features. Domain association is also different between the subsets. The subsets show organism as well as domain‐based clustering, suggestive of propagation by both duplication and horizontal transfer events. Structure‐based sequence analysis of the subsets led to the identification of common structural and sequence motifs in the HNH family with the other three families under the His‐Me endonuclease superfamily.
Protein flexibility and intrinsic disorder
Authors: Radivojac Predrag , Obradovic Zoran , Smith David K. , Zhu Guang , Vucetic Slobodan , Brown Celeste J. , Lawson J. David , Dunker A. Keith 
Published: December 2003

AbstractComparisons were made among four categories of protein flexibility: (1) low‐B‐factor ordered regions, (2) high‐B‐factor ordered regions, (3) short disordered regions, and (4) long disordered regions. Amino acid compositions of the four categories were found to be significantly different from each other, with high‐B‐factor ordered and short disordered regions being the most similar pair. The high‐B‐factor (flexible) ordered regions are characterized by a higher average flexibility index, higher average hydrophilicity, higher average absolute net charge, and higher total charge than disordered regions. The low‐B‐factor regions are significantly enriched in hydrophobic residues and depleted in the total number of charged residues compared to the other three categories. We examined the predictability of the high‐B‐factor regions and developed a predictor that discriminates between regions of low and high B‐factors. This predictor achieved an accuracy of 70% and a correlation of 0.43 with experimental data, outperforming the 64% accuracy and 0.32 correlation of predictors based solely on flexibility indices. To further clarify the differences between short disordered regions and ordered regions, a predictor of short disordered regions was developed. Its relatively high accuracy of 81% indicates considerable differences between ordered and disordered regions. The distinctive amino acid biases of high‐B‐factor ordered regions, short disordered regions, and long disordered regions indicate that the sequence determinants for these flexibility categories differ from one another, whereas the significantly‐greater‐than‐chance predictability of these categories from sequence suggest that flexible ordered regions, short disorder, and long disorder are, to a significant degree, encoded at the primary structure level.
On the analysis of membrane protein circular dichroism spectra
Authors: Sreerama Narasimha , Woody Robert W. 
Published: December 2003

AbstractAnalysis of circular dichroism spectra of proteins provides information about protein secondary structure. Analytical methods developed for such an analysis use structures and spectra of a set of reference proteins. The reference protein sets currently in use include soluble proteins with a wide range of secondary structures, and perform quite well in analyzing CD spectra of soluble proteins. The utility of soluble protein reference sets in analyzing membrane protein CD spectra, however, has been questioned in a recent study that found current reference protein sets to be inadequate for analyzing membrane proteins. We have examined the performance of reference protein sets available in the CDPro software package for analyzing CD spectra of 13 membrane proteins with available crystal structures. Our results indicate that the reference protein sets currently available for CD analysis perform reasonably well in analyzing membrane protein CD spectra, with performance indices comparable to those for soluble proteins. Soluble + membrane protein reference sets, which were constructed by combining membrane proteins with soluble protein reference sets, gave improved performance in both soluble and membrane protein CD analysis.
Expression and biochemical characterization of two small heat shock proteins from the thermoacidophilic crenarchaeon Sulfolobus tokodaii strain 7
Authors: Usui Keisuke , Ishii Noriyuki , Kawarabayasi Yutaka , Yohda Masafumi 
Published: December 2003

AbstractWe expressed and characterized two sHsps, StHsp19.7 and StHsp14.0, from a thermoacidophilic crenarchaeon, Sulfolobus tokodaii strain 7. StHsp19.7 forms a filamentous structure consisting of spherical particles and lacks molecular chaperone activity. Fractionation of Sulfolobus extracts by size exclusion chromatography with immunoblotting indicates that StHsp19.7 exists as a filamentous structure in vivo. On the other hand, StHsp14.0 exists as a spherical oligomer like other sHsps. It showed molecular chaperone activity to protect thermophilic 3‐isopropylmalate dehydrogenase (IPMDH) from thermal aggregation at 87°C. StHsp14.0 formed variable‐sized complexes with denatured IPMDH at 90°C. Using StHsp14.0 labeled with fluorescence or biotin probe and magnetic separation, subunit exchanges between complexes were demonstrated. This is the first report on the filament formation of sHsp and also the high molecular chaperone activity of thermophilic archaeal sHsps.
Detection of homologous proteins by an intermediate sequence search
Authors: John Bino , Sali Andrej 
Published: December 2003

AbstractWe developed a variant of the intermediate sequence search method (ISSnew) for detection and alignment of weakly similar pairs of protein sequences. ISSnew relates two query sequences by an intermediate sequence that is potentially homologous to both queries. The improvement was achieved by a more robust overlap score for a match between the queries through an intermediate. The approach was benchmarked on a data set of 2369 sequences of known structure with insignificant sequence similarity to each other (BLAST E‐value larger than 0.001); 2050 of these sequences had a related structure in the set. ISSnew performed significantly better than both PSI‐BLAST and a previously described intermediate sequence search method. PSI‐BLAST could not detect correct homologs for 1619 of the 2369 sequences. In contrast, ISSnew assigned a correct homolog as the top hit for 121 of these 1619 sequences, while incorrectly assigning homologs for only nine targets; it did not assign homologs for the remainder of the sequences. By estimate, ISSnew may be able to assign the folds of domains in ∼29,000 of the ∼500,000 sequences unassigned by PSI‐BLAST, with 90% specificity (1 − false positives fraction). In addition, we show that the 15 alignments with the most significant BLAST E‐values include the nearly best alignments constructed by ISSnew.
Helix formation and the unfolded state of a 52‐residue helical protein
Authors: Cao Wei , Bracken Clay , Kallenbach Neville R. , Lu Min 
Published: December 2003

AbstractA growing class of proteins in biological processes has been found to be unfolded on isolation under normal solution conditions. We have used NMR spectroscopy to characterize the structural and dynamic properties of the unfolded and partially folded states of a 52‐residue alanine‐rich protein (Ala‐14) at temperatures from −5°C to 40°C. At 40°C, alanine residues in Ala‐14 adopt ϕ and ψ angles, consistent with a significant ensemble population of polyproline II conformation. Analysis of relaxation rates in the protein reveals that a series of residues, Gln 35–Ala 36–Ala 37–Lys 38–Asp 39–Asp 40–Ala 41–Ala 42, displays slow motional dynamics at both −5°C and 40°C. Temperature‐dependent chemical shift changes indicate that this region is the site of helix initiation. The remaining N‐terminal residues become increasingly dynamic as they extend from the nucleation site. The C terminus remains dynamic and changes less with temperature, indicating it is relatively unstructured. Ala‐14 provides a high‐resolution portrait of the unfolded state and the process of helix nucleation and propagation in the absence of tertiary contacts, information that bears on early events in protein folding.