bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spontaneously immortalized human T lymphocytes develop gain of chromosomal region 2p13–24 as an early and common genetic event
Authors: Siwicki Jan Konrad , Berglund Mattias , Rygier Jolanta , Pienkowska‐Grela Barbara , Grygalewicz Beata , Degerman Sofie , Golovleva Irina , Chrzanowska Krystyna H. , Lagercrantz Svetlana , Blennow Elisabeth , Roos Göran , Larsson Catharina 
Published: June 2004

AbstractTo gain further insight into the molecular events responsible for the extended life span and immortalization of human lymphoid cells, we analyzed a series of spontaneously immortalized, IL2‐dependent human T‐cell lines using molecular cytogenetic techniques. Two of the cell lines were derived from normal spleen and three from patients with Nijmegen breakage syndrome (NBS), a recessive disorder characterized by a high incidence of lymphoid malignancies. Here we show that spontaneous immortalization of the five T‐cell lines was associated with the acquisition of copy number gains involving chromosomal region 2p13–24 as common early alterations. In addition, we found an amplification of 8q21–24 after prolonged propagations in all three NBS‐derived cell lines as well as early development of near‐tetraploidy in two of these lines. Gains involving the short arm of chromosome 2 recently were found in several lymphoid malignancies. Therefore, the cell lines described here can be used for identification and characterization of genes involved in the pathogenesis of lymphoid neoplasms and would also provide a useful tool for better understanding the mechanisms responsible for cell immortalization. © 2004 Wiley‐Liss, Inc.
Mapping of a translocation breakpoint in a Peutz–Jeghers hamartoma to the putative PJS locus at 19q13.4 and mutation analysis of candidate genes in polyp and STK11‐negative PJS cases
Authors: Hearle Nicholas , Lucassen Anneke , Wang Rubin , Lim Wendy , Ross Fiona , Wheeler Robert , Moore Isabella , Shipley Janet , Houlston Richard 
Published: June 2004

AbstractGerm‐line mutations in the serine‐threonine kinase gene STK11 (LKB1) cause Peutz–Jeghers syndrome (PJS), a rare autosomal dominantly inherited disease, characterized by hamartomatous polyposis and mucocutaneous pigmentation. STK11 mutations only account for about half of PJS cases, and a second disease locus has been proposed at chromosome segment 19q13.4 on the basis of genetic linkage analysis in one family. We identified a t(11;19)(q13;q13.4) in a PJS polyp arising from the small bowel in a female infant age 6 days. Because the breakpoint in 19q13.4 may disrupt the putative PJS disease gene mapping to this region, we mapped the breakpoint and analyzed DNA from the case and a series of STK11‐negative PJS cases. Using two‐color interphase fluorescence in situ hybridization, the breakpoint region was refined to a 0.5‐Mb region within 19q13.4. Eight candidate genes mapping to the breakpoint region—U2AF2, EPN1, NALP4, NALP11, NALP5, ZNF444, PTPRH, and KIAA1811—were screened for mutations in germ‐line and polyp DNA from the case and from 15 PJS cases that did not harbor germ‐line STK11 mutations. No pathogenic mutations in the candidate genes were identified. This report provides further evidence of the existence of a second PJS disease locus at 19q13.4 and excludes involvement of eight candidate genes. © 2004 Wiley‐Liss, Inc.
Computational constraints between retrieving the past and predicting the future, and the CA3‐CA1 differentiation
Authors: Treves Alessandro 
Published: June 2004

AbstractThe differentiation between the CA3 and CA1 fields of the mammalian hippocampus is one of the salient traits that set it apart from the organization of the homologue medial wall in reptiles and birds. CA3 is widely thought to function as an autoassociator, but what do we need CA1 for? Based on evidence for a specific role of CA1 in temporal processing, I have explored the hypothesis that the differentiation between CA3 and CA1 may help solve a computational conflict. The conflict is between pattern completion, or integrating current sensory information on the basis of memory, and prediction, or moving from one pattern to the next in a stored sequence. CA3 would take care of the former, while CA1 would concentrate on the latter. I have found the hypothesis to be only weakly supported by neural network simulations. The conflict indeed exists, but two mechanisms that would relate more directly to a functional CA3‐CA1 differentiation were found unable to produce genuine prediction. Instead, a simple mechanism based on firing frequency adaptation in pyramidal cells was found to be sufficient for prediction, with the degree of adaptation as the crucial parameter balancing retrieval with prediction. The differentiation between the architectures of CA3 and CA1 has a minor but significant, and positive, effect on this balance. In particular, for a fixed anticipatory interval in the model, it increases significantly the information content of hippocampal outputs. There may therefore be just a simple quantitative advantage in differentiating the connectivity of the two fields. Moreover, different degrees of adaptation in CA3 and CA1 cells were not found to lead to better performance, further undermining the notion of a functional dissociation. © 2004 Wiley‐Liss, Inc.
Coherent structures in a fully developed stage of a non‐isothermal round jet
Authors: Suto Hitoshi , Matsubara Koji , Kobayashi Mutsuo , Watanabe Hidehito , Matsudaira Yusaku 
Published: June 2004

AbstractDirect numerical simulation (DNS) was performed for a non‐isothermal air jet with a Reynolds number of 1200 in order to reveal coherent structures of the developed jet. A fourth‐order central finite difference was applied to the simulation. An effort was also made to enable experimental visualization (dye mixing and PTV) to support the validity of the instantaneous structures by DNS. Computational results for two types of inlet profiles suggested that nozzle conditions scarcely affect the turbulence statistics and the coherent structures in a jet‐established stage. Two‐point correlations of velocity and temperature show that similar distributions denoting the temperature can be used as an indicator of a vortex. A conceptual model of a hairpin‐shaped vortex was proposed and validated by two‐point correlations and PDF analysis for vortex alignment. The hairpin‐shaped vortex stands with legs inclined downstream. The inclination angle and the tilting angle between the two legs are −45° and 40°, respectively. © 2004 Wiley Periodicals, Inc. Heat Trans Asian Res, 33(5): 342–356, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.20014
Simulation of coherent structures in turbulent boundary layer using Gao–Yong equations of turbulence
Authors: Liu Bo , Gao Ge , Yong Yan 
Published: June 2004

AbstractThe equations of incompressible turbulent flow developed by the Gao–Yong turbulence model have two important features. First, they do not contain any empirical coefficients or wall functions. Second, the series representation of turbulence energy equation reflects multi‐scale structures of the nonlinearity of turbulence, and, therefore, is capable of describing both statistical mean flows and the coherent structures. This paper presents some simulation results of a two‐dimensional turbulent boundary layer with zero pressure gradient based on Gao–Yong equations of turbulence. With a staggered grid arrangement, an incompressible SIMPLE code was used in the simulations. The simulated coherent structures have verified the adaptability of the newly derived equations to real intermittent turbulent flows. The effect of the orders of the energy equation and computational grid scales on the detection of coherent structures is also investigated. © 2004 Wiley Periodicals, Inc. Heat Trans Asian Res, 33(5): 287–298, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.20019
Downregulation of the antiapoptotic MCL‐1 protein and apoptosis in MA‐11 breast cancer cells induced by an anti‐epidermal growth factor receptor–Pseudomonas exotoxin a immunotoxin
Authors: Andersson Yvonne , Juell Siri , Fodstad Øystein 
Published: June 2004

AbstractPseudomonas exotoxin (PE)–containing immunotoxins (ITs) act by arresting protein synthesis and promoting apoptosis, but the mechanisms of the induced apoptosis and the relationship to protein synthesis inhibition is not well elucidated. We studied these effects in MA‐11 human breast cancer cells treated with 425.3PE, an unmodified PE covalently linked to the 425.3 antibody, which targets the EGF receptor. This IT induced efficient inhibition of protein synthesis with simultaneous induction of apoptosis. Thus, treatment of cells with 10 ng/ml of IT for 5 hr caused 85% inhibition of protein synthesis in parallel with caspase‐3, ‐8 and ‐9 activation and PARP inactivation. Even after 72 hr of IT treatment, preincubation with the broad‐spectrum caspase inhibitor z‐VAD‐FMK caused a significant increase in cell survival without affecting IT‐induced protein synthesis inhibition. Interestingly, a combination of z‐VAD‐FMK and the cathepsin B/L inhibitor z‐FA‐FMK prevented completely IT‐induced cell death in MA‐11 cells after 24 hr, indicating that cathepsin activation may be important for optimal induction of IT‐induced cell death. IT treatment caused after 2.5 hr a significant decrease in the level of the antiapoptotic protein Mcl‐1 but not of Bcl‐2 and Bcl‐XL. Furthermore, Mcl‐1 expression was not sensitive to caspase inhibitors but was totally prevented by the lactacystin proteasome inhibitor, suggesting that IT‐induced apoptosis may be triggered by a reduction in the Mcl‐1 level. Mitochondrial membrane potential (ΔΨ mito) decreased concurrently with caspase activation, showing the involvement of ΔΨ mito as a regulator of IT‐induced apoptosis. Our results demonstrate that 425.3PE‐mediated cell death involves simultaneous induction of apoptosis and protein synthesis inhibition in MA‐11 cells, thus contributing to an understanding of the mechanisms involved in IT‐induced apoptosis. © 2004 Wiley‐Liss, Inc.
Perineal talc exposure and epithelial ovarian cancer risk in the Central Valley of California
Authors: Mills Paul K. , Riordan Deborah G. , Cress Rosemary D. , Young Heather A. 
Published: June 2004

AbstractPerineal talc use has been suggested as a possible risk factor for ovarian cancer based on its structural similarity to asbestos, a known human carcinogen. A population‐based epidemiologic case‐control study of epithelial ovarian cancer (EOC) was conducted in 22 counties of Central California that comprise the reporting area for 2 regional cancer registries. Telephone interviews were conducted with 256 cases diagnosed in the years 2000–2001 and 1,122 controls frequency‐matched on age and ethnicity. The interview obtained information on demographic factors, menstrual and reproductive experience, exogenous hormone use, surgical history and family history of cancer. Questions on perineal talc use included frequency of use, duration of use and specific years when talc was used. Multivariate‐adjusted odds ratio (OR) and 95% confidence intervals (CI) were derived from unconditional logistic regression. The OR for ever use of talc was 1.37 (CI = 1.02–1.85) compared to never users. However, no dose response association was found. Tubal ligation (TL) modified the effect of talc on EOC such that women with TL had an OR of 0.88 (CI = 0.46–1.68) associated with perineal talc use, whereas women with no TL had an OR of 1.54 (CI = 1.10–2.16). Talc use and EOC risk was highest in women with serous invasive tumors (OR = 1.77; CI = 1.12–2.81). This study provides some support for the hypothesis that perineal talc use is associated with an increased risk of EOC. © 2004 Wiley‐Liss, Inc.
Lipid phosphate phosphatases and related proteins: Signaling functions in development, cell division, and cancer
Authors: Brindley David N. 
Published: June 2004

AbstractLipid phosphates initiate key signaling cascades in cell activation. Lysophosphatidate (LPA) and sphingosine 1‐phosphate (S1P) are produced by activated platelets. LPA is also formed from circulating lysophosphatidylcholine by autotaxin, a protein involved tumor progression and metastasis. Extracellular LPA and S1P stimulate families of G‐protein coupled receptors that elicit diverse responses. LPA is involved in wound repair and tumor growth. Exogenous S1P is a potent stimulator of angiogenesis, a process vital in development, tissue repair and the growth of aggressive tumors. Inside the cell, phosphatidate (PA), ceramide 1‐phosphate (C1P), LPA, and S1P act as signaling molecules with distinct functions including the stimulation of cell division, cytoskeletal rearrangement, Ca2+ transients, and membrane movement. These observations imply that phosphatases that degrade lipid phosphates on the cell surface, or inside the cell, regulate cell signaling under physiological and pathological conditions. This occurs through attenuation of signaling by the lipid phosphates and by the production of bioactive products (diacylglycerol, ceramide, and sphingosine). Three lipid phosphate phosphatases (LPPs) and a splice variant dephosphorylate LPA, PA, CIP, and S1P. Two S1P phosphatases (SPPs) act specifically on S1P. In addition, there is family of four LPP‐related proteins (LPRs, or plasticity‐related genes, PRGs). PRG‐1 expression in neurons has been reported to increase extracellular LPA breakdown and attenuate LPA‐induced axonal retraction. It is unclear whether the LRPs dephosphorylate LPA directly, stimulate LPP activity, or bind LPA and S1P. Also, the importance of extra‐ versus intra‐cellular actions of the LPPs and SPPs, and the individual roles of different isoforms is not firmly established. Understanding the functions and regulation of the LPPs, SPPs and related proteins will hopefully contribute to interventions to correct dysfunctions in conditions such as wound repair, inflammation, angiogenesis, tumor growth, and metastasis. © 2004 Wiley‐Liss, Inc.
Ime2p and Cdc28p: Co‐pilots driving meiotic development
Authors: Honigberg Saul M. 
Published: June 2004

AbstractMeiosis can be considered an elaboration of the cell division cycle in the sense that meiosis combines cell‐cycle processes with programs specific to meiosis. Each phase of the cell division cycle is driven forward by cell‐cycle kinases (Cdk) and coordinated with other phases of the cycle through checkpoint functions (Hartwell and Weinert [1989]: Science. 246:629–634). Meiotic differentiation is also controlled by these two types of regulation (Murakami and Nurse [2000]: Biochem J. 349:1–12; Roeder and Bailis [2000]: Trends Genet. 16:395–403); however, recent study in the budding yeast S. cerevisiae indicates that progression of meiosis is also controlled by a master regulator specific to meiosis, namely the Ime2p kinase (Benjamin et al. [2003]: Genes Dev. 17:1–16; Schindler et al. [2003]: Mol Cell Biol 23:8718–8728). Below, I describe the overlapping roles of Ime2p and Cdk during meiosis in yeast and speculate on how these two kinases cooperate to drive the progression of meiosis. © 2004 Wiley‐Liss, Inc.
Post‐transcriptional control of expression of sFlt‐1, an endogenous inhibitor of vascular endothelial growth factor
Authors: Huckle William R. , Roche Rebecca I. 
Published: June 2004

AbstractVascular endothelial growth factor (VEGF) is a major modulator of angiogenesis. Biological effects of VEGF are mediated by endothelial cell‐surface receptors, KDR and Flt‐1. Alternative Flt‐1 RNA processing, involving retention of intron 13 and the use of intronic cleavage‐polyadenylation signals, produces a secreted form of Flt‐1, “sFlt‐1,” that binds VEGF with high affinity and can inhibit VEGF signaling. To probe mechanisms controlling sFlt‐1 expression, we have cloned and sequenced Flt‐1 intron 13 from a mouse genomic library and located RNA processing signals potentially involved in sFlt‐1 mRNA formation. A minigene construct containing Flt‐1 intron 13 directed the expression of both secreted (i.e., cleaved/polyadenylated) and transmembrane (i.e., spliced) forms of Flt‐1 mRNA and protein. Using rapid amplification of 3′ cDNA ends (3′‐RACE) and quantitative PCR (QPCR) analysis to test the activity of intronic cleavage‐polyadenylation signals, we observed that multiple sites were utilized for sFlt‐1 mRNA processing in both native tissues and Flt‐1 minigene transfectants. In transfectants, the most distal signal was utilized preferentially. The potential for interaction between pathways leading to sFlt‐1 or full‐length Flt‐1 was evaluated using QPCR to measure relevant mRNAs after transfection with signal mutants. Decreased expression of sFlt‐1 mRNA in cleavage‐polyadenylation mutants was accompanied by reciprocal increases in full‐length Flt‐1 mRNA. Multiple sFlt‐1 mRNA species are formed that differ by up to 3.9 kb in their 3′‐untranslated regions (UTRs), which contain sites of potential regulatory importance. The reciprocity between sFlt‐1 and Flt‐1 mRNA expression suggests a novel post‐transcriptional mechanism by which sFlt‐1 protein production and, thereby, responsiveness to VEGF, may be modulated. © 2004 Wiley‐Liss, Inc.
Synthesis, separation and biodistribution of 99mTc‐CO‐MIBI complex
Authors: Hao Gui Yang , Zang Jian Ying , Zhu Lin , Guo Yu Zhi , Liu Bo Li 
Published: June 2004

Abstract99mTc‐CO‐MIBI was prepared by a two‐step procedure involving the convenient preparation of the [99mTc(CO)3(OH2)3]+ precursor and followed by the substitution of the water molecules by the MIBI (2‐methoxyisobutylisonitrile) ligands. In a second step, the reaction solution was adjusted to different pH values, and then the product, 99mTc‐CO‐MIBI, was confirmed to be a mixture of two complexes: complex A and complex B, whose labeling yields could be over 90%. The ratio of complex B to the sum of A and B could increase gradually from 0 to 1 when pH was shifted from 3.0 to 9.0. These changes were monitored by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). The two complexes were stable within 8 h at room temperature in vitro. The partition coefficient of the two complexes indicated that there was distinct difference between them. Biodistribution in mice demonstrated that complex B showed better myocardial imaging properties than that of complex A. The heart/liver ratios of complex A, the mixture, and complex B were 1.57, 1.93, and 2.33, respectively, for 30 min post‐injection. The discovery of chemical and biological properties of 99mTc‐CO‐MIBI would certainly promote the research on a new promising myocardial perfusion‐imaging agent. Copyright © 2004 John Wiley & Sons, Ltd.
Profiling of sulfoconjugates in urine by using precursor ion and neutral loss scans in tandem mass spectrometry. Application to the investigation of heavy metal toxicity in rats
Authors: Lafaye Alexandra , Junot Christophe , Ramounet‐Le Gall Béatrice , Fritsch Paul , Ezan Eric , Tabet Jean‐Claude 
Published: June 2004

AbstractThis paper reports a liquid chromatographic/electrospray ionization mass spectrometric (LC/ESI‐MS) method for profiling a wide range of structurally different sulfoconjugated compounds in urine and its application to the characterization of biomarkers for heavy metal toxicity in rat urine. Sulfoconjugates were first isolated by solid‐phase extraction and the LC separation was performed on a reversed‐phase column. Sulfoconjugates were detected in a triple‐quadrupole mass spectrometer by simultaneously monitoring constant losses of 80 u (or 80 Th for doubly charged ions), precursors of m/z 80 (SO3−•) and precursors of m/z 97 $(\hbox{HSO}_{4}^{-})$. The ESI‐MS detection conditions were optimized on dehydroepiandrosterone sulfate and estradiol sulfate and tested on other sulfoconjugates. The analysis of urine samples from humans and rats by using the developed method allowed the detection of about 15 peaks in each mode of detection. It was then applied to the investigation of heavy metal toxicity in rats. Comparative analysis of the chromatographic fingerprints of urine from control and uranium‐ and cadmium‐treated rats showed several variations in the chromatographic pattern of the sulfoconjugates. Diagnostic m/z ratios were confirmed by analyzing individual urine samples and one of the observed variations seemed to be specific to uranium toxicity. The ion responsible for this variation has been identified as 4‐ethylphenol sulfate by comparison of its chromatographic retention time and collision‐induced dissociation mass spectra (MS2 and MS3 performed on a quadrupole ion trap instrument) with those of the synthesized compound. Copyright © 2004 John Wiley & Sons, Ltd.
Gas‐phase ion chemistry of the allene–phosphine and silane–allene–phosphine systems
Authors: Operti Lorenza , Rabezzana Roberto , Turco Francesca , Vaglio Gian Angelo 
Published: June 2004

AbstractThe gas‐phase ion chemistry of allene–phosphine and silane–allene–phosphine mixtures was studied by ion trap mass spectrometry. Rate constants of the main processes were measured and compared with the collisional rate constants to determine the reaction efficiencies. For the binary mixture, the highest yield of C‐ and P‐containing ions is obtained with a 1 : 1 partial pressure ratio among the reagents. In the ternary mixture, formation of ion species containing Si, C and P together is mainly achieved in reactions of Si/P ions with allene, with a lower contribution from reactions of Si/C and C/P ions with phosphine and silane, respectively. The formation of ternary ion clusters is related to their possible role as precursors of amorphous silicon carbides doped with phosphorus, obtained by deposition from properly activated silane–allene–phosphine mixtures. Copyright © 2004 John Wiley & Sons, Ltd.
Gas‐phase ion chemistry in the ternary silane–propyne–phosphine system
Authors: Operti Lorenza , Rabezzana Roberto , Turco Francesca , Vaglio Gian Angelo 
Published: June 2004

AbstractThe gas‐phase ion chemistry of propyne–phosphine and silane–propyne–phosphine mixtures was studied by ion trap mass spectrometry. For the binary mixture, the effect of different partial pressures of the reagents on the yield of C and P‐containing ions was evaluated. Reaction sequences and rate constants were determined and reaction efficiencies were calculated from comparison of experimental and collisional rate constants. In the ternary silane–propyne–phosphine systems, the reaction pathways leading to formation of SimCnPpHq+ ions were determined and the rate constants of the most important steps were measured. For some ion species, selected by double isolation procedures (MS/MS), the low ion abundances prevented determination of the reaction rate constants. Si, C and P‐containing ions are mainly produced in reactions of SimPpHq+ ions with propyne, while the reactivity of the SimCnHq+ ions towards PH3 and of the CnPpHq+ ions towards SiH4 is very low. The formation of hydrogenated SiCP ions is interesting for their possible role as precursors of amorphous silicon carbides doped with phosphorus, obtained in a single step, by deposition from properly activated silane–propyne–phosphine mixtures. Copyright © 2004 John Wiley & Sons, Ltd.