bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenetic marks by DNA methylation specific to stem, germ and somatic cells in mice
Authors: Shiota Kunio , Kogo Yasushi , Ohgane Jun , Imamura Takuya , Urano Atsushi , Nishino Koichiro , Tanaka Satoshi , Hattori Naka 
Published: March 2003

AbstractBackground:  DNA methylation is involved in many gene functions such as gene‐silencing, X‐inactivation, imprinting and stability of the gene. We recently found that some CpG islands had a tissue‐dependent and differentially methylated region (T‐DMR) in normal tissues, raising the possibility that there may be more CpG islands capable of differential methylation.Results:  We investigated the genome‐wide DNA methylation pattern of CpG islands by restriction landmark genomic scanning (RLGS) in mouse stem cells (ES, EG and trophoblast stem) before and after differentiation, and sperm as well as somatic tissues. A total of 247 spots out of 1500 (16%) showed differences in the appearance of their RLGS profiles, indicating that CpG islands having T‐DMR were numerous and widespread. The methylation pattern was specific, and varied in a precise manner according to cell lineage, tissue type and during cell differentiation.Conclusions:  Genomic loci with altered methylation status seem to be more common than has hitherto been realized. The formation of DNA methylation patterns at CpG islands is one of the epigenetic events which underlies the production of various cell types in the body. These findings should have implications for the use of embryonic stem cells and cells derived from them therapeutically, and also for the cloning of animals by the transfer of somatic cell nuclei.
Generation of human artificial chromosomes expressing naturally controlled guanosine triphosphate cyclohydrolase I gene
Authors: Ikeno Masashi , Inagaki Hidehito , Nagata Keiko , Morita Miwa , Ichinose Hiroshi , Okazaki Tuneko 
Published: March 2003

AbstractBackground Human artificial chromosomes (HACs) are generated from the precursor DNA constructs containing α‐satellite DNA with CENP‐B boxes, and the process could be used for the incorporation of large genes in the HACs. Guanosine triphosphate cyclohydrolase I (GCH1) is the first and rate‐limiting enzyme for the biosynthesis of tetrahydrobiopterin, the essential co‐factor of aromatic amino acid hydroxylases and nitric oxide synthase.Results: We constructed HACs carrying a 180 kb genome segment encoding the human GCH1 gene and its control region from the bacterial artificial chromosome (BAC) with the GCH1 segment by co‐transfection with the α‐satellite DNA‐containing BAC to a human fibroblast cell line. Two cell lines carrying a HAC with GCH1 genes were obtained. Both HACs were composed of multiple copies of precursor BACs and were maintained stably in human and mouse cell lines. The GCH1 activities of the HAC‐carrying human fibroblast cell lines were elevated but still highly sensitive to IFN‐γ induction, mimicking the response of the gene expression from the authentic chromosomal genes.Conclusion: These HACs will provide a useful system for analysis of the complex regulatory circuit of the GCH1 gene in vivo and also function as a tool for gene delivery in animal models or in therapeutic trials.
The yeast kinetochore protein Slk19 is required to prevent aberrant chromosome segregation in meiosis and mitosis
Authors: Pfiz Stefan , Zimmermann Johann , Hilt Wolfgang 
Published: March 2003

AbstractBackground Slk19 is a coiled‐coil protein, which locates to the kinetochores of S. cerevisiae. Most cells lacking Slk19 undergo incomplete meiosis and form dyads during sporulation. Endogenous chromosomes appeared to be predominantly divided in an equational manner during single‐division meiosis of slk19 null mutants.Results: We have monitored the segregation of artificial chromosomes (YACs) in slk19 null mutants during both single‐division meiosis and complete meiosis. In contrast to the results obtained with endogenous chromosomes, YACs only rarely undergo equational segregation during single division meiosis, although high rates of aberrant segregation were detected. This accounts for the high frequency of lethal spores among dyads of slk19Δ null mutants. The fraction of slk19Δ cells that were able to form tetrads solely exhibited YAC segregation defects in meiosis II, whereas the segregation of YACs in meiosis I was normal in these cells. This result might indicate that correct chromosome division in meiosis I is a prerequisite for tetrad formation. slk19 null mutants also showed YAC instability in mitosis and reduced survival after the induction of mitotic spindle damage.Conclusion: Slk19 is required to avoid aberrant segregation of chromosomes in meiosis I and II and in mitosis. We suggest that the absence of Slk19 leads to uncoupling of chromosome movement from completion of microtubule attachment and resolution of chromosome cohesion.
Mouse GSPT2, but not GSPT1, can substitute for yeast eRF3 in vivo
Authors: Le Goff Catherine , Zemlyanko Olga , Moskalenko Svetlana , Berkova Nadia , Inge‐Vechtomov Sergei , Philippe Michel , Zhouravleva Galina 
Published: March 2003

AbstractBackground The termination of protein synthesis in eukaryotes involves at least two polypeptide release factors (eRFs), eRF1 and eRF3. In mammals two genes encoding eRF3 structural homologues were identified and named GSPT1 and GSPT2.Results: In the present study, we demonstrate that mouse mGSPT2 but not mGSPT1 could functionally substitute the essential yeast gene SUP35. However, we show that the complementation property of mGSPT1 protein is modified when NH2‐tagged by GST. Since mGSPT1 and mGSPT2 differ mainly in their N‐terminal regions, we developed a series of N‐terminal deleted constructs and tested them for complementation in yeast. We found that at least amino acids spanning 84–120 of mGSPT1 prevent the complementation of sup35 mutation. The fact that chimeras between mGSPT1, mGSPT2 and yeast Sup35 complement the disruption of the SUP35 gene indicates that the N‐terminal region of mGSPT1 is not sufficient by itself to prevent complementation. Complementation of the mutant with a double disruption of SUP35 and SUP45 genes is obtained when mGSPT2 and human eRF1 are co‐expressed but not by co‐expression of mGSPT1 and human eRF1.Conclusions: Our results strongly suggest that the two proteins (mGSPT1 and mGSPT2) are different. We hypothesize that the full length mGSPT1 does not have the properties expected for eRF3.
Densin‐180, a synaptic protein, links to PSD‐95 through its direct interaction with MAGUIN‐1
Authors: Ohtakara Kazuhiro , Nishizawa Miwako , Izawa Ichiro , Hata Yutaka , Matsushima Satoshi , Taki Waro , Inada Hiroyasu , Takai Yoshimi , Inagaki Masaki 
Published: March 2003

AbstractBackground: Densin‐180, a brain‐specific protein highly concentrated at the postsynaptic density (PSD), belongs to the LAP [leucine‐rich repeats and PSD‐95/Dlg‐A/ZO‐1 (PDZ) domains] family of proteins, some of which play fundamental roles in the establishment of cell polarity.Results: To identify new Densin‐180‐interacting proteins, we screened a yeast two‐hybrid library using the COOH‐terminal fragment of Densin‐180 containing the PDZ domain as bait, and we isolated MAGUIN‐1 as a Densin‐180‐binding protein. MAGUIN‐1, a mammalian homologue of Drosophila connector enhancer of KSR (CNK), is known to interact with PSD‐95 and has a short isoform, MAGUIN‐2. The Densin‐180 PDZ domain bound to the COOH‐terminal PDZ domain‐binding motif of MAGUIN‐1. Densin‐180 co‐immunoprecipitated with MAGUIN‐1 as well as with PSD‐95 from the rat brain. In dissociated hippocampal neurones Densin‐180 co‐localized with MAGUINs and PSD‐95, mainly at neuritic spines. In transfected cells, Densin‐180 formed a ternary complex with MAGUIN‐1 and PSD‐95, whereas no association was detected between Densin‐180 and PSD‐95 in the absence of MAGUIN‐1. MAGUIN‐1 formed a dimer or multimer via the COOH‐terminal leucine‐rich region which is present in MAGUIN‐1 but not in ‐2. Among the PDZ domains of PSD‐95, the first was sufficient for interaction with MAGUIN‐1.Conclusion: These results suggest that the potential to dimerize or multimerize allows MAGUIN‐1 to bind simultaneously to both Densin‐180 and PSD‐95, leading to the ternary complex assembly of these proteins at the postsynaptic membrane.
A minigene containing four discrete cis elements recapitulates GATA‐1 gene expression in vivo
Authors: Ohneda Kinuko , Shimizu Ritsuko , Nishimura Shigeko , Muraosa Yasushi , Takahashi Satoru , Engel James Douglas , Yamamoto Masayuki 
Published: March 2003

AbstractBackground:  The GATA‐1haematopoietic enhancer (G1HE), located between 3.9 and 2.6 kb 5′ to the haematopoietic first exon, is essential for GATA‐1 gene transcription in erythroid cells. However, G1HE is not sufficient to confer tissue specificity on the GATA‐1 gene in vivo, indicating that additional regulatory sequences are necessary.Results: We demonstrate here that two other upstream promoter elements containing a double GATA motif or two CACCC boxes are also indispensable for reporter gene expression in erythroid cells in the transgenic mouse. The combination of these three cis‐acting regions was sufficient for reporter expression in primitive erythroid cells, as demonstrated by linking the elements together into a 659 bp artificial (GdC) minigene. The minigene activated the transcription of a reporter gene from either the endogenous or an exogenous thymidine kinase promoter, retaining cell type‐specificity. The addition of a 320 bp fragment in the first intron to the GdC minigene sustained reporter expression in the definitive stage. Moreover, a line of transgenic mouse that expressed GATA‐1 cDNA under the control of the complete 979 bp minigene rescued GATA‐1 germ line mutant mice from embryonic lethality.Conclusions: A combination of four distinct sequence motifs co‐operatively serve as a fundamental functional unit for GATA‐1 erythroid transcription in vivo.
Taxilin; a novel syntaxin‐binding protein that is involved in Ca2+‐dependent exocytosis in neuroendocrine cells
Authors: Nogami Satoru , Satoh Sachie , Nakano Michiko , Shimizu Hiroaki , Fukushima Hiromichi , Maruyama Ayumi , Terano Akira , Shirataki Hiromichi 
Published: March 2003

AbstractBackground:  The syntaxin family is a central coordinator and participates in multiple protein–protein interactions in the soluble N‐ethyl maleimide‐sensitive factor attachment protein receptor machinery, which is involved in intracellular vesicle traffic. However, the molecular mechanism by which the syntaxin family regulates intracellular vesicle transport is not well known.Results:  We have identified and purified a novel binding partner of syntaxin‐3 from rat lung, and isolated and sequenced the cDNA of its human homologue from a human brain cDNA library. The cDNA had an open reading frame encoding a protein of 546 amino acids with a calculated Mr of 61 890. We tentatively referred to this protein as taxilin. A structural analysis of taxilin revealed the existence of an extraordinarily long coiled‐coil domain in its C‐terminal half. Syntaxin‐1a and ‐4, as well as syntaxin‐3 interacted with taxilin, but syntaxin‐7 or ‐8 did not. Northern blot analysis showed that taxilin was ubiquitously expressed. Over‐expression of full‐length taxilin inhibited Ca2+‐dependent exocytosis in PC12 cells.Conclusions:  These results indicate that taxilin is a novel binding partner of several syntaxin family members and suggest that taxilin is involved in Ca2+‐dependent exocytosis in neuroendocrine cells.
Mitogen‐activated protein kinase p38 defines the common senescence‐signalling pathway
Authors: Iwasa Hiroaki , Han Jiahuai , Ishikawa Fuyuki 
Published: March 2003

AbstractBackground: Cellular senescence is a state of irreversible growth arrest shown by normal cells, and has been most extensively studied in replicative senescence caused by telomere shortening. Several conditions, including oncogenic Ras over‐expression and inappropriate culture conditions, also induce senescence without telomere shortening. However, it remains unclear how a common set of senescence phenotypes is indistinguishably induced in various types of senescence.Results: We demonstrate that p38 mitogen‐activated protein kinase (MAPK) plays important causative roles in senescent cells following telomere shortening, Ras‐Raf activation, oxidative stress or inappropriate culture conditions. By monitoring the kinetics of p38 activation, we suggest that p38 is activated not directly by the initial stimuli, but in response to unidentified cellular conditions caused by these stimuli. Importantly, this p38‐activating condition appears to be defined quantitatively as a sum of continuous and low‐level stresses, and remains even after the initial stimuli are withdrawn, which may explain the well‐known irreversible nature of cellular senescence. We also show that papilloma virus E7 abolishes the p38‐induced growth arrest but not other senescence‐associated phenotypes, indicating the differential role of pRb in the downstream of p38.Conclusion: These results indicate that p38 comprises the senescence‐executing pathway in response to diverse stimuli.
Synaptic localization of SAPAP1, a synaptic membrane‐associated protein
Authors: Yao Ikuko , Iida Junko , Nishimura Wataru , Hata Yutaka 
Published: March 2003

AbstractBackground: SAPAP1 was originally identified as a protein interacting with the guanylate kinase domain of PSD‐95. SAPAP1 also interacts with various proteins, including neurofilaments, synaptic scaffolding molecule (S‐SCAM), nArgBP2, dynein light chain and Shank through different regions.Results: We expressed various regions of SAPAP1 in hippocampal neurones. The synaptic targeting of SAPAP1 was mediated by the N‐terminal region and did not depend on the interaction with PSD‐95 or S‐SCAM. SAPAP1 was not involved in the synaptic localization of PSD‐95 or S‐SCAM, but affected that of Shank. The synaptic targeting of SAPAP1 was not suppressed by blocking NMDA or AMPA receptors. Fluorescent recovery after a photobleaching study revealed that SAPAP1 was immobile at synapses.Conclusion: SAPAP1 is a component of the static core of PSD, and its dynamics are different from those of the other PSD components, PSD‐95, S‐SCAM and BEGAIN.
Non-linear inversion using general measures of data misfit and model structure
Authors: Farquharson Colin G. , Oldenburg Douglas W. 
Published: March 2003

Abstract
We investigate the use of general, non-l 2 measures of data misfit and model structure in the solution of the non-linear inverse problem. Of particular interest are robust measures of data misfit, and measures of model structure which enable piecewise-constant models to be constructed. General measures can be incorporated into traditional linearized, iterative solutions to the non-linear problem through the use of an iteratively reweighted least-squares (IRLS) algorithm. We show how such an algorithm can be used to solve the linear inverse problem when general measures of misfit and structure are considered. The magnetic stripe example of Parker (1994) is used as an illustration. This example also emphasizes the benefits of using a robust measure of misfit when outliers are present in the data. We then show how the IRLS algorithm can be used within a linearized, iterative solution to the non-linear problem. The relevant procedure contains two iterative loops which can be combined in a number of ways. We present two possibilities. The first involves a line search to determine the most appropriate value of the trade-off parameter and the complete solution, via the IRLS algorithm, of the linearized inverse problem for each value of the trade-off parameter. In the second approach, a schedule of prescribed values for the trade-off parameter is used and the iterations required by the IRLS algorithm are combined with those for the linearized, iterative inversion procedure. These two variations are then applied to the 1-D inversion of both synthetic and field time-domain electromagnetic data.
Bounds on the complex conductivity of geophysical mixtures
Authors: Tripp Alan C. , Cherkaeva Elena , Hulen Jeff 
Published: March 2003

Following previous work on bounds for complex dielectrics, bounds on the complex conductivity of a mixture of two isotropic components can be developed which are independent of any special assumption concerning the geometry of the mixture. If certain broad restrictions are assumed, such as isotropy of the mixture, then the bounds can be made more restrictive. These bounds reveal the range of the induced polarization response which can be caused by a mixture of two materials of known complex conductivity. The bounds can also be generalized for spectral responses. The bounds are conservative lithologically in the sense that many of the special models corresponding to boundary responses have lithological counterparts.The chief use for the given bounds is to gain insight into the nature of the induced polarization response. It is also possible to use the bounds to estimate the volume fractions of the components. We illustrate how this is done for the case of a general anisotropic medium.
Modelling of local velocity anomalies: a cookbook
Authors: Juliard Corinne , Thore Pierre D. 
Published: March 2003

The determination of small‐scale velocity anomalies (from tens to a few hundreds of metres) is a major problem in seismic exploration. The impact of such anomalies on a structural interpretation can be dramatic and conventional techniques such as tomographic inversion or migration velocity analysis are powerless to resolve the ambiguity between structural and velocity origins of anomalies. We propose an alternative approach based on stochastic modelling of numerous anomalies until a set of models is found which can explain the real data. This technique attempts to include as much a priori geological information as possible. It aims at providing the interpreter with a set of velocity anomalies which could possibly be responsible for the structural response. The interpreter can then choose one or several preferred models and pursue a more sophisticated analysis. The class of retained models are all equivalent in terms of data and therefore represent the uncertainty in the model space.The procedure emulates the real processing sequence using a simplified scheme. Essentially, the technique consists of five steps: 1 Interpretation of a structural anomaly in terms of a velocity anomaly with its possible variations in terms of position, size and amplitude. 2 Drawing a model by choosing the parameters of the anomaly within the acceptable range. 3 Modelling the traveltimes in this model and producing the imaging of the reflected interface. 4 Comparing the synthetic data with the real data and keeping the model if it lies within the data uncertainty range. 5 Iterate from step 2.In order to avoid the high computational cost inherent in using statistical determinations, simplistic assumptions have been made:• The anomaly is embedded in a homogeneous medium: we assume that the refraction and the time shift due to the anomaly have a first‐order effect compared with ray bending in the intermediate layers.• We model only the zero‐offset rays and therefore we restrict ourselves to structural problems.• We simulate time migration and so address only models of limited structural complexity.These approximations are justified in a synthetic model which includes strong lateral velocity variations, by comparing the result of a full processing sequence (prestack modelling, stack and depth migration) with the simplified processing. This model is then used in a blind test on the inversion scheme.
Dip moveout of converted waves and parameter estimation in transversely isotropic media
Authors: Tsvankin Ilya , Grechka Vladimir 
Published: March 2003

For transverse isotropy with a vertical symmetry axis (VTI media), P‐wave reflection data alone are insufficient for building velocity models in depth. Here, we show that all parameters of VTI media responsible for propagation of P‐ and SV‐waves (the P‐wave and S‐wave vertical velocities VP0 and VS0 and the anisotropic parameters ε and δ) can be obtained by combining P‐wave traveltimes with the moveout of PS‐waves converted at a horizontal and dipping interface. Using converted modes, rather than pure S‐waves, avoids the need for expensive shear‐wave excitation on land and makes the method suitable for offshore exploration.The inversion algorithm is based on a new analytic description of the dip moveout of PS‐waves developed for symmetry planes of anisotropic media (and for any vertical plane in models with weak azimuthal anisotropy). The common‐midpoint (CMP) traveltime–offset relationship, derived in a parametric form and represented through the components of the slowness vector of the P‐ and S‐waves, makes it possible to compute the moveout curve of the PS‐wave without two‐point ray tracing. This formalism also leads to closed‐form solutions for moveout attributes, such as the coordinates (xmin, tmin) of the traveltime minimum, the normal‐moveout (NMO) velocity defined at x = xmin and the slope of the moveout curve (apparent slowness) at zero offset.The parameter‐estimation algorithm operates with reflection moveout of P‐ and PS‐waves from a horizontal and dipping reflector. The NMO velocities of P‐ and PS‐waves from horizontal events and the ratio of the corresponding zero‐offset traveltimes yield three equations for the four unknown medium parameters. The remaining parameter is found from an overdetermined system of equations that includes the P‐wave NMO velocity and moveout attributes of the PS‐wave for a dipping event. Numerical analysis shows that the PS‐wave dip‐moveout signature plays a crucial role in obtaining accurate estimates of the anisotropic parameters. The joint inversion of P and PS data provides the necessary information not only for P‐wave depth imaging in VTI media, but also for the processing of PS‐waves, including re‐sorting of PS traces into common‐reflection‐point gathers and transformation to zero offset (TZO).