bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recruitment of topoisomerase I (Scl‐70) to nucleoplasmic proteasomes in response to xenobiotics suggests a role for altered antigen processing in scleroderma
Authors: Chen Min , Dittmann Assemgul , Kuhn Annegret , Ruzicka Thomas , Mikecz Anna von 
Published: March 2005

AbstractObjectiveScleroderma, also known as systemic sclerosis (SSc), is a chronic, life‐threatening autoimmune disease characterized by a wide spectrum of manifestations and a variable evolution. The presence of particular antinuclear antibodies is often predictive of the clinical expression and prognosis of the disease, but the molecular mechanisms of the immune responses remain unclear. Recently, we have shown xenobiotic‐induced recruitment of nuclear autoantigens to proteasomes in the cell nucleus in cell culture and in animal models in correlation with a unique autoantibody response. In this study, we attempted to validate our findings in patients with SSc.MethodsUsing indirect immunofluorescence microscopy, run‐on replication and transcription assays, immunoblotting, and proteasome activity assays, we analyzed the nuclear structure, function, and proteasomal proteolysis in HEp‐2 cells treated with xenobiotics or left untreated. Blood dendritic cells (DCs) were isolated from 30 patients with SSc and age‐ and sex‐matched control subjects to determine the subcellular localization of SSc autoantigens in relation to proteasomes.ResultsXenobiotics induced a relocation of the SSc autoantigen DNA topoisomerase I (Scl‐70, topo I) to nucleoplasmic clusters, where proteasomes degrade topo I. Colocalization of topo I with proteasomes occurred exclusively in DCs from patients with SSc who developed antibodies against this autoantigen. Neither centromeres nor other SSc autoantigens colocalized with proteasomes in DCs from patients with SSc or from control subjects.ConclusionAlteration of nuclear structure and function by xenobiotics induces recruitment of the nuclear autoantigen topo I for proteasomal processing. This event may, in turn, lead to subsequent presentation of the resulting peptides on the cell surface and the autoimmune responses against topo I in SSc.
Protein name tagging guidelines: lessons learned
Authors: Mani Inderjeet , Hu Zhangzhi , Jang Seok Bae , Samuel Ken , Krause Matthew , Phillips Jon , Wu Cathy H. 
Published: March 2005

AbstractInterest in information extraction from the biomedical literature is motivated by the need to speed up the creation of structured databases representing the latest scientific knowledge about specific objects, such as proteins and genes. This paper addresses the issue of a lack of standard definition of the problem of protein name tagging. We describe the lessons learned in developing a set of guidelines and present the first set of inter‐coder results, viewed as an upper bound on system performance. Problems coders face include: (a) the ambiguity of names that can refer to either genes or proteins; (b) the difficulty of getting the exact extents of long protein names; and (c) the complexity of the guidelines. These problems have been addressed in two ways: (a) defining the tagging targets as protein named entities used in the literature to describe proteins or protein‐associated or ‐related objects, such as domains, pathways, expression or genes, and (b) using two types of tags, protein tags and long‐form tags, with the latter being used to optionally extend the boundaries of the protein tag when the name boundary is difficult to determine. Inter‐coder consistency across three annotators on protein tags on 300 MEDLINE abstracts is 0.868 F‐measure. The guidelines and annotated datasets, along with automatic tools, are available for research use. Copyright © 2005 John Wiley & Sons, Ltd.
Genomic analyses of transport proteins inRalstonia metallidurans
Authors: von Rozycki Torsten , Nies Dietrich H. , Saier Milton H. 
Published: March 2005

AbstractRalstonia (Wautersia, Cupriavidus) metallidurans(Rme) is better able to withstand high concentrations of heavy metals than any other well‐studied organism. This fact renders it a potential agent of bioremediation as well as an ideal model organism for understanding metal resistance phenotypes. We have analysed the genome of Rme for genes encoding homologues of established and putative transport proteins; 13% of all genes in Rme encode such homologues. Nearly one‐third of the transporters identified (32%) appear to function in inorganic ion transport with three‐quarters of these acting on cations. Transporters specific for amino acids outnumber sugar transporters nearly 3 : 1, and this fact plus the large number of uptake systems for organic acids indicates the heterotrophic preferences of these bacteria. Putative drug efflux pumps comprise 10% of the encoded transporters, but numerous efflux pumps for heavy metals, metabolites and macromolecules were also identified. The results presented should facilitate genetic manipulation and mechanistic studies of transport in this remarkable bacterium. Copyright © 2005 John Wiley & Sons, Ltd.
Ontology‐based interactive information extraction from scientific abstracts
Authors: Milward David , Bjäreland Marcus , Hayes William , Maxwell Michelle , Öberg Lisa , Tilford Nick , Thomas James , Hale Roger , Knight Sylvia , Barnes Julie 
Published: March 2005

AbstractOver recent years, there has been a growing interest in extracting information automatically or semi‐automatically from the scientific literature. This paper describes a novel ontology‐based interactive information extraction (OBIIE) framework and a specific OBIIE system. We describe how this system enables life scientists to make ad hoc queries similar to using a standard search engine, but where the results are obtained in a database format similar to a pre‐programmed information extraction engine. We present a case study in which the system was evaluated for extracting co‐factors from EMBASE and MEDLINE. Copyright © 2005 John Wiley & Sons, Ltd.
Monastrol, a selective inhibitor of the mitotic kinesin Eg5, induces a distinctive growth profile of dendrites and axons in primary cortical neuron cultures
Authors: Yoon Seung Yong , Choi Jung Eun , Huh Jae‐Wan , Hwang Onyou , Lee Hui Sun , Hong Hea Nam , Kim Donghou 
Published: March 2005

AbstractVarious factors including some motor proteins regulate microtubule (MT) transport and influence the formation of neuronal processes. Eg5, a slow and non‐processive (+)‐end directed motor molecule, is expressed in developing and differentiated neurons. However, how Eg5 works in neurons is still elusive. Thus, we treated primary rat cortical neuron cultures with monastrol, a specific inhibitor of Eg5, to investigate its role in neurons. Immature neurons treated with monastrol extended longer processes than control within a few hours. After 3 days, immature neurons treated with monastrol had longer dendrites but slightly shorter axons than control. This difference in growth between dendrites and axons became more prominent as the cells differentiated until 5 days. Interestingly, MT distributions in the cell bodies of monastrol‐treated neurons appeared somewhat circular surrounding the nucleus, while MTs in the cell bodies of control neurons were primarily distributed in the MT organizing center (MTOC) just beside the nucleus. In mature neurons, monastrol treatment induced the axonal clusters of tubulins, grossly not affecting dendrites. Taken together, we conclude that Eg5 acts distinctively on dendrites and axons in neurons and suggest a putative model of how Eg5 works distinctively on dendrites and axons. Cell Motil. Cytoskeleton 60:181–190, 2005. © 2005 Wiley‐Liss, Inc.
Preparing to move: Assembly of the MSP amoeboid motility apparatus during spermiogenesis in Ascaris
Authors: Rodriguez Maria Antonia , LeClaire Lawrence L. , Roberts Thomas M. 
Published: March 2005

AbstractWe exploited the rapid, inducible conversion of non‐motile Ascaris spermatids into crawling spermatozoa to examine the pattern of assembly of the MSP motility apparatus that powers sperm locomotion. In live sperm, the first detectable motile activity is the extension of spikes and, later, blebs from the cell surface. However, examination of cells by EM revealed that the formation of surface protrusions is preceded by assembly of MSP filament tails on the membranous organelles in the peripheral cytoplasm. These organelle‐associated filament meshworks assemble within 30 sec after induction of spermiogenesis and persist until the membranous organelles are sequestered into the cell body when the lamellipod extends. The filopodia‐like spikes, which are packed with bundles of filaments, extend and retract rapidly but last only a few seconds before giving way to, or converting into, blebs. Coalescence of these blebs, each supported by a dense mesh of filaments, often initiates lamellipod extension, which culminates in the formation of the robust, dynamic MSP fiber complexes that generate sperm motility. The same membrane phosphoprotein that orchestrates assembly of the fiber complexes at the leading edge of the lamellipod of mature sperm is also found at all sites of filament assembly during spermiogenesis. The orderly progression of steps that leads to construction of a functional motility apparatus illustrates the precise spatio‐temporal control of MSP filament assembly in the developing cell and highlights the remarkable similarity in organization and plasticity shared by the MSP cytoskeleton and the actin filament arrays in conventional crawling cells. Cell Motil. Cytoskeleton 60:191–199, 2005 © 2005 Wiley‐Liss, Inc.
Through versus Cross Electron Delocalization in Polytriacetylene Oligomers: A Computational Analysis
Authors: Bruschi Maurizio , Giuffreda Maria Grazia , Lüthi Hans Peter 
Published: March 2005

AbstractHerein, we report a systematic theoretical investigation of the molecular and electronic properties of unsubstituted polytriacetylene (PTA) and iso‐polytriacetylene (iso‐PTA) oligomers, which are characterized by through and cross π‐conjugation pathways, respectively. The goal of the study is to compare through versus cross conjugation on the basis of the computed molecular geometries of the neutral, anionic, and cationic species, the electron affinities, ionization potentials, excitation energies, and nonlinear optical properties for oligomers up to the nonamer. Differences in the effective conjugation length are directly related to electron delocalization in cross‐ and through‐conjugated pathways.	As in the through‐conjugated oligomers, that is, the PTAs, the frontier orbitals of the iso‐PTA oligomers are delocalized along the entire carbon backbone, suggesting that π‐delocalization can extend through cross‐linked carbon atoms. However, in contrast to the PTA oligomers, the bond lengths remain strictly constant and the reduction of the energy gap beyond the trimer is completely due to the correlation contribution. On the other hand, in the anions and cations, the bond lengths do change significantly with increasing chain length. Therefore, oxidation or reduction of the iso‐PTA oligomer appears to switch on delocalization through cross‐linked carbon atoms. Obviously, the effective conjugation length is specific and depends on the observable considered.
Pressure Effects on Friedel–Crafts Alkylation Reactions in Supercritical Difluoromethane
Authors: Abbott Andrew P. , Corr Stuart , Durling Nicola E. , Hope Eric G. 
Published: March 2005

AbstractDielectrometry is used as a novel technique for following the rate of a Friedel–Crafts alkylation reaction in supercritical (sc) difluoromethane. Although the process was not optimized, good product yields were obtained and reaction rates were found to be larger than in CO2 at comparable conditions. The reaction order is determined using the initial rate method and the reaction is shown to be first‐order with respect to both anisole and t‐butyl chloride. The reaction rate constant is unaffected by pressures above 120 bar but close to the critical pressure the value decreases with increasing pressure. It is also shown that the product distribution for the alkylation of anisole shows significant pressure dependence with substitution at the ortho‐position being favored at lower pressures, which is ascribed to hydrogen bonding. This pressure dependency is not observed in sc CO2 or using toluene as a substrate, which supports the idea that hydrogen bonding may be important in the reaction mechanism. The effect of the different reagents and temperature on the rate of the alkylation reaction was also determined.
Focal‐Point Conformational Analysis of Ethanol, Propanol, and Isopropanol
Authors: Kahn Kalju , Bruice Thomas C. 
Published: March 2005

AbstractConformational analysis of three small alcohols—ethanol, propanol, and isopropanol—was carried out by systematically improving the basis set and the level of electron correlation. Correlation energy contributions to conformational energies are strongly basis‐set‐dependent but accurate energy contributions can be obtained by extrapolation to the basis‐set limit. At the basis‐set limit, second‐ and third‐order electron correlation effects play a significant role for rotations around the CCOH, HCCO, and CCCO bonds. Specifically, second‐ and third‐order correlation effects strongly stabilize structures in which the hydroxylic hydrogen eclipses with the adjacent carbon; a lesser stabilization is present in structures where the CCOH moiety is in the gauche form. Fourth‐order correlation effects to the CCOH rotation are small due to a partial cancellation of the singles, doubles, and quadruples contribution by the triples contribution. Electron correlation significantly lowers barriers for methyl‐group rotations in ethanol and isopropanol, and in these cases the fourth‐order correlation effects are noticeable. The relatively large overall importance of third‐order correlation energy contributions raises a concern that the inability to accurately estimate this slowly converging contribution may become a limiting factor when highly accurate conformational energies in larger molecules are sought.
Simultaneous AFM Manipulation and Fluorescence Imaging of Single DNA Strands
Authors: Hards Andrew , Zhou Chunqing , Seitz Markus , Bräuchle Christoph , Zumbusch Andreas 
Published: March 2005

AbstractWe report combined atomic force and far‐field fluorescence microscopic experiments which allow the simultaneous atomic force manipulation and optical observation of individual dye‐labeled DNA molecules. A detailed understanding of the binding properties of DNA to different transparent surfaces is prerequisite for these investigations. Atomic force spectroscopy and fluorescence microscopy of single DNA strands yielded detailed insight into two different types of DNA binding onto transparent polylysine‐coated and silanized glass surfaces. We subsequently demonstrate how the different binding can be exploited to perform two types of nanomanipulation experiments: On polylysine, strong electrostatic interactions over the whole length of the DNA strand enable the writing of micrometer‐sized patterns. By contrast, the strong pointwise attachment of DNA to silanized surfaces allows horizontal stretching of single DNA strands to lengths exceeding 1.6 times the contour length of the DNA strand. With this new approach it is possible to directly observe the rupture of the strongly bonded DNA strand.
MLL is fused to EB1 (MAPRE1), which encodes a microtubule‐associated protein, in a patient with acute lymphoblastic leukemia
Authors: Fu Jen‐Fen , Hsu Hui‐Chin , Shih Lee‐Yung 
Published: March 2005

AbstractWe have shown that the EB1 (MAPRE1) gene, at 20q11.2, is fused to MLL in an adult patient with pro‐B acute lymphoblastic leukemia. Southern blot analysis indicated that a rearrangement of the MLL gene was involved in the chromosomal abnormality. cDNA panhandle polymerase chain reaction (PCR) identified the fusion transcript, in which MLL exon 6 was fused in‐frame with EB1 exon 5. The presence of the MLL–EB1 and the reciprocal EB1–MLL fusion transcripts was verified by reverse‐transcription PCR. EB1 is the first gene on chromosome 20 found to fuse with MLL. The genomic break junctions of MLL–EB1 and EB1–MLL were amplified by long‐distance PCR. Sequencing of the break junctions revealed that multiple DNA breaks had occurred and that the DNA fragments flanked by these breaks had been duplicated, deleted, or inverted. Nontemplate DNA segments of 2 bp also were detected at the breakpoints on derivative chromosomes 11 and 20. These features indicate that this translocation likely resulted from the DNA damage‐repair pathway. EB1 is a microtubule‐associated protein that interacts with the colorectal adenomatous polyposis coli tumor‐suppressor protein and plays important roles in regulating microtubule dynamics, cell polarity, and chromosome stability. Immunofluorescence staining demonstrated that the MLL–EB1 fusion proteins were localized in the nuclei. © 2005 Wiley‐Liss, Inc.
Ductal breast carcinoma develops through different patterns of chromosomal evolution
Authors: Molist Romain , Gerbault‐Seureau Michele , Sastre‐Garau Xavier , Sigal‐Zafrani Brigitte , Dutrillaux Bernard , Muleris Martine 
Published: March 2005

AbstractIn a previous study that used comparative genomic hybridization (CGH) to analyze 43 ductal breast carcinomas selected for hyperdiploidy, we proposed the existence of two distinct pathways of chromosomal evolution. In the present study, in which we reassessed our cytogenetic findings on 158 ductal breast carcinomas selected for having a modal number of chromosomes of fewer than 60, we confirmed the existence of two subtypes of tumors. Along with the great majority of tumors (142 of 158) that evolved through structural rearrangements with no or very few whole‐chromosome gains, we found that a minor subset (16 of 158) evolved through progressive gains of whole chromosomes with no or only a few associated rearrangements. In this article, we describe the karyotypes of these 16 tumors together with data from CGH, which was performed for 10 of them. Chromosomes 5, 7, 8, and 20 were the most frequently gained. Our findings support the evidence of a new pathway of chromosomal evolution in a small subset of ductal breast carcinomas characterized by numerical chromosome aberrations. © 2005 Wiley‐Liss, Inc.
Genetic and epigenetic alterations of the candidate tumor‐suppressor gene MYO18B, on chromosome arm 22q, in colorectal cancer
Authors: Nakano Tetsuhiro , Tani Masachika , Nishioka Michiho , Kohno Takashi , Otsuka Ayaka , Ohwada Susumu , Yokota Jun 
Published: March 2005

AbstractAllelic imbalance (AI) on chromosome arm 22q has been detected in 20%–40% of colorectal cancers, suggesting that this chromosome arm has a tumor‐suppressor gene involved in colorectal carcinogenesis. Recently, we isolated a candidate tumor‐suppressor gene, MYO18B, at 22q12.1, that is deleted, mutated, and hypermethylated in more than 50% of lung cancers. In the present study, we analyzed genetic and epigenetic alterations of the MYO18B gene in colorectal cancers. AI at the MYO18B locus was detected in 16 of 43 (40%) informative cases. Mutations of the MYO18B gene were detected in 2 of 11 (18%) cell lines and 1 of 47 (2%) surgical specimens. Nine of 11 (82%) cell lines showed reduced MYO18B expression, which was restored in all 9 by treatment with 5‐aza‐2′‐deoxycytidine and/or trichostatin A (TSA). Although hypermethylation of the promoter CpG island for MYO18B was not detected, a significant correlation was observed between the level of MYO18B expression and the level of acetylation of histones H3 and H4 in 6 cell lines with and without TSA treatment. Thus, it was suggested that MYO18B is inactivated in a considerable fraction of colorectal cancers by several mechanisms, especially silencing by histone deacetylation and/or AI. Furthermore, restoration of MYO18B expression in colorectal cancer cell lines HT29 and DLD‐1 suppressed anchorage‐independent growth, whereas it did not affect the growth rate in vitro. These results suggest that genetic and epigenetic inactivation of the MYO18B gene play an important role in colorectal carcinogenesis. © 2005 Wiley‐Liss, Inc.
NY‐ESO‐1/LAGE‐1 coexpression with MAGE‐A cancer/testis antigens: A tissue microarray study
Authors: Bolli Martin , Schultz‐Thater Elke , Zajac Paul , Guller Ulrich , Feder Chantal , Sanguedolce Francesca , Carafa Vincenza , Terracciano Luigi , Hudolin Tvrtko , Spagnoli Giulio C. , Tornillo Luigi 
Published: March 2005

AbstractThe characterization of the expression pattern of different families of cancer/testis (C/T) antigens in different tumors, at the protein level, might be of relevance in the development of multiantigen vaccine preparations for active specific immunotherapy. We have used tissue microarray (TMA) technology to explore in large numbers of tumor specimens the expression of NY‐ESO‐1/LAGE‐1 C/T antigens and its correlation with MAGE‐A expression by using D8.38 and 57B monoclonal antibodies (MAb). The epitopes recognized by these reagents in C/T antigens were identified by molecular mapping by using a bacterial expression system. Out of 2,052 samples, 119 (5.8%) scored positive upon staining with D8.38 NY‐ESO‐1/LAGE‐1‐specific MAb. Expression in >10% of cases was detectable in melanoma and basalioma (31.6 and 18.2%, respectively), large cell carcinomas and adenocarcinomas of the lung (17.8 and 10.5%, respectively), stomach adenocarcinomas of the intestinal type (13.2%), pT2‐4 bladder TCC (18.2%), nonseminomatous carcinomas of the testis (10.4%) and liposarcomas (15.4%). Simultaneous expression of NY‐ESO‐1/LAGE‐1 and MAGE‐A C/T antigens was then addressed in a TMA where 101/845 and 73/845 samples (12 and 8.6%, respectively) showed evidence of MAGE‐A or NY‐ESO‐1/LAGE‐1 specific staining, respectively. In 35/845 specimens (4.1%) concomitant expression of MAGE‐A and NY‐ESO‐1/LAGE‐1 was observed (p = 0.0002). Discrepancies in the expression of NY‐ESO‐1/LAGE‐1 and MAGE‐A were conspicuously detectable in squamous cell carcinomas of the skin (MAGE‐A positive but NY‐ESO‐1/LAGE‐1 negative) and in liposarcomas (NY‐ESO‐1/LAGE‐1 positive, but MAGE‐A negative). Taken together, these data suggest novel areas of application of C/T antigens targeted active specific immunotherapy possibly based on multiantigen vaccine preparations. © 2005 Wiley‐Liss, Inc.
Estimation of the absolute internal‐rotation entropy of molecules with two torsional degrees of freedom from stochastic simulations
Authors: Darian Eva , Hnizdo Vladimir , Fedorowicz Adam , Singh Harshinder , Demchuk Eugene 
Published: March 2005

AbstractA method of statistical estimation is applied to the problem of evaluating the absolute entropy of internal rotation in a molecule with two torsional degrees of freedom. The configurational part of the entropy is obtained as that of the joint probability density of an arbitrary form represented by a two‐dimensional Fourier series, the coefficients of which are statistically estimated using a sample of the torsional angles of the molecule obtained by a stochastic simulation. The internal rotors in the molecule are assumed to be attached to a common frame, and their reduced moments of inertia are initially calculated as functions of the two torsional angles, but averaged over all the remaining internal degrees of freedom using the stochastic‐simulation sample of the atomic configurations of the molecule. The torsional‐angle dependence of the reduced moments of inertia can be also averaged out, and the absolute internal‐rotation entropy of the molecule is obtained in a good approximation as the sum of the configurational entropy and a kinetic contribution fully determined by the averaged reduced moments of inertia. The method is illustrated using Monte Carlo simulations of isomers of stilbene and halogenated derivatives of propane. The two torsional angles in cis‐stilbene are found to be much more strongly correlated than those in trans‐stilbene, while the degree of the angular correlation in propane increases strongly on substitution of hydrogen atoms with chlorine. © 2005 Wiley Periodicals, Inc. J Comput Chem 26: 651–660, 2005