658 research outputs found

    Regulation of mouse Scgb3a1 gene expression by NF-Y and association of CpG methylation with its tissue-specific expression

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    <p>Abstract</p> <p>Background</p> <p>Secretoglobin (SCGB) 3A1 is a secretory protein of small molecular weight with tumor suppressor function. It is highly expressed in lung and trachea in both human and mouse, with additional tissues expressing the protein that differ depending on the species. However, little is known about the function and transcriptional regulation of this gene in normal mouse tissues.</p> <p>Results</p> <p>By reporter gene transfection and gel mobility shift analyses, we demonstrated that expression of the mouse <it>Scgb3a1 </it>gene is regulated by a PU-box binding protein and a ubiquitous transcription factor NF-Y that respectively binds to the PU-boxes located at -99 to -105 bp and -158 to -164 bp, and the "CCAAT" binding sites located at -425 to -429 bp and -498 to -502 bp from the transcription start site of the gene. However, the effect of PU-box binding protein on transcriptional activation is minimal as compared to NF-Y, suggesting that NF-Y is a more critical transcription factor for mouse <it>Scgb3a1 </it>gene transcription. Despite that NF-Y is a ubiquitous factor, <it>Scgb3a1 </it>is highly expressed only in mouse lung and mtCC cells that are derived from SV40 transformed mouse Clara cells, but not in ten other mouse tissues/cells examined. Gene methylation analysis revealed that within 600 bp of the <it>Scgb3a1 </it>gene promoter region, there are nine CpG methylation sites present, of which two CpGs closest to the transcription start site of the gene are unmethylated in the tissues/cells expressing SCGB3A1.</p> <p>Conclusion</p> <p>A ubiquitous transcription factor NF-Y binds to and activates expression of the mouse <it>Scgb3a1 </it>gene and tissue-specific expression of the gene is associated with CpG methylation of the promoter.</p

    Gravitational Lens Statistics and The Density Profile of Dark Halos

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    We investigate the influence of the inner profile of lens objects on gravitational lens statistics taking into account of the effect of magnification bias and both the evolution and the scatter of halo profiles. We take the dark halos as the lens objects and consider the following three models for the density profile of dark halos; SIS (singular isothermal sphere), the NFW (Navarro Frenk White) profile, and the generalized NFW profile which has a different slope at smaller radii. The mass function of dark halos is assumed to be given by the Press-Schechter function. We find that magnification bias for the NFW profile is order of magnitude larger than that for SIS. We estimate the sensitivity of the lensing probability of distant sources to the inner profile of lenses and to the cosmological parameters. It turns out that the lensing probability is strongly dependent on the inner density profile as well as on the cosmological constant. We compare the predictions with the largest observational sample, the Cosmic Lens All-Sky Survey. The absence or presence of large splitting events in larger surveys currently underway such as the 2dF and SDSS could set constraints on the inner density profile of dark halos.Comment: 22 pages, minor changes and references added, accepted for publication in Ap

    Presenilin-dependent intramembrane cleavage of ephrin-B1

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    BACKGROUND: Presenilin-dependent γ-secretase cleavage of several transmembrane proteins, including amyloid-β precursor protein and Notch, mediates the intramembrane proteolysis to liberate their intracellular domains that are involved in cellular signaling. Considering γ-secretase inhibitors as therapeutics for Alzheimer's disease, understanding the physiologically and biologically important substrate for γ-secretase activity in brains is emerging issue. To elucidate the molecular mechanism and physiological role of γ-secretase, we screened candidate molecules for γ-secretase substrates. RESULTS: We show that ephrin-B1, that participates in cell-cell repulsive and attractive signaling together with its Eph receptor, constitutively undergoes ectodomain shedding and that the residual membrane-tethered fragment is sequentially cleaved by γ-secretase to release the intracellular domain. Furthermore, overexpression of membrane-tethered ephrin-B1 caused protrusion of numerous cellular processes consisted of F-actin, that required the preservation of the most C-terminal region of ephrin-B1. In contrast, soluble intracellular domain translocated into the nucleus and had no effect on cell morphology. CONCLUSION: Our findings suggest that ephrin-B is a genuine substrate for γ-secretase and regulates the cytoskeletal dynamics through intramembrane proteolysis

    HybGFS: a hybrid method for genome-fingerprint scanning

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    BACKGROUND: Protein identification based on mass spectrometry (MS) has previously been performed using peptide mass fingerprinting (PMF) or tandem MS (MS/MS) database searching. However, these methods cannot identify proteins that are not already listed in existing databases. Moreover, the alternative approach of de novo sequencing requires costly equipment and the interpretation of complex MS/MS spectra. Thus, there is a need for novel high-throughput protein-identification methods that are independent of existing predefined protein databases. RESULTS: Here, we present a hybrid method for genome-fingerprint scanning, known as HybGFS. This technique combines genome sequence-based peptide MS/MS ion searching with liquid-chromatography elution-time (LC-ET) prediction, to improve the reliability of identification. The hybrid method allows the simultaneous identification and mapping of proteins without a priori information about their coding sequences. The current study used standard LC-MS/MS data to query an in silico-generated six-reading-frame translation and the enzymatic digest of an entire genome. Used in conjunction with precursor/product ion-mass searching, the LC-ETs increased confidence in the peptide-identification process and reduced the number of false-positive matches. The power of this method was demonstrated using recombinant proteins from the Escherichia coli K12 strain. CONCLUSION: The novel hybrid method described in this study will be useful for the large-scale experimental confirmation of genome coding sequences, without the need for transcriptome-level expression analysis or costly MS database searching

    Artificial neural network approach for selection of susceptible single nucleotide polymorphisms and construction of prediction model on childhood allergic asthma

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    BACKGROUND: Screening of various gene markers such as single nucleotide polymorphism (SNP) and correlation between these markers and development of multifactorial disease have previously been studied. Here, we propose a susceptible marker-selectable artificial neural network (ANN) for predicting development of allergic disease. RESULTS: To predict development of childhood allergic asthma (CAA) and select susceptible SNPs, we used an ANN with a parameter decreasing method (PDM) to analyze 25 SNPs of 17 genes in 344 Japanese people, and select 10 susceptible SNPs of CAA. The accuracy of the ANN model with 10 SNPs was 97.7% for learning data and 74.4% for evaluation data. Important combinations were determined by effective combination value (ECV) defined in the present paper. Effective 2-SNP or 3-SNP combinations were found to be concentrated among the 10 selected SNPs. CONCLUSION: ANN can reliably select SNP combinations that are associated with CAA. Thus, the ANN can be used to characterize development of complex diseases caused by multiple factors. This is the first report of automatic selection of SNPs related to development of multifactorial disease from SNP data of more than 300 patients

    Successful Treatment of Cardiac Diffuse Large B-cell Lymphoma : A Report of Two Cases

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    Cardiac lymphoma is a rare neoplasm of the heart,defined as an extranodal lymphoma exclusively located in the heart and/or pericardium. Multiple imaging modalities may help to diagnose cardiac tumors ; however, pathological diagnosis is difficult because of the limited approaches for obtaining tissue samples. This report describes two cases of prompt histological diagnosis of cardiac lymphoma as diffuse large B-cell type and their successful treatment with chemotherapy. Immunohistochemical analyses revealed one case as CD5-positive and the other as CD5-negative lymphoma. This report highlights the necessity of histological diagnosis and the importance of clinicopathological characterization of cardiac lymphoma. Shinshu Med J 59 : 177―183, 2011 (Received for publication January 7, 2011; accepted in revised form February 16, 2011)Article信州医学雑誌 59(3): 177-183(2011)departmental bulletin pape

    A novel non-canonical Notch signaling regulates expression of synaptic vesicle proteins in excitatory neurons

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    Notch signaling plays crucial roles for cellular differentiation during development through γ-secretase-dependent intramembrane proteolysis followed by transcription of target genes. Although recent studies implicate that Notch regulates synaptic plasticity or cognitive performance, the molecular mechanism how Notch works in mature neurons remains uncertain. Here we demonstrate that a novel Notch signaling is involved in expression of synaptic proteins in postmitotic neurons. Levels of several synaptic vesicle proteins including synaptophysin 1 and VGLUT1 were increased when neurons were cocultured with Notch ligands-expressing NIH3T3 cells. Neuron-specific deletion of Notch genes decreased these proteins, suggesting that Notch signaling maintains the expression of synaptic vesicle proteins in a cell-autonomous manner. Unexpectedly, cGMP-dependent protein kinase (PKG) inhibitor, but not γ-secretase inhibitor, abolished the elevation of synaptic vesicle proteins, suggesting that generation of Notch intracellular domain is dispensable for this function. These data uncover a ligand-dependent, but γ-secretase-independent, non-canonical Notch signaling involved in presynaptic protein expression in postmitotic neurons

    Expressions of the cytochrome P450 monooxygenase gene Cyp4g1 and its homolog in the prothoracic glands of the fruit fly Drosophila melanogaster (Diptera: Drosophilidae) and the silkworm Bombyx mori (Lepidoptera: Bombycidae)

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    Here we describe the expression profiles of the cytochrome P450 monooxygenase gene Cyp4g1 in the fruit fly, Drosophila melanogaster Meigen, and its homolog in the silkworm, Bombyx mori L. We identified Cyp4g1 by a microarray analysis to examine the expression levels of 86 predicted D. melanogaster P450 genes in the ring gland that contains the prothoracic gland (PG), an endocrine organ responsible for synthesizing ecdysteroids. B. mori Cyp4g25 is a closely related homolog of D. melanogaster Cyp4g1 and is also expressed in the PG. A developmental expression pattern of Cyp4g25 in the PG is positively correlated with a fluctuation in hemolymph ecdysteroid titer in the late stage of the final instar. Moreover, the expression of Cyp4g25 in cultured PGs is significantly induced by the addition of prothoracicotropic hormone (PTTH), a neuropeptide hormone that stimulates the synthesis and release of ecdysone. We propose that Cyp4g1 and Cyp4g25 are the candidates that play a role in regulating PG function and control ecdysteroid production and/or metabolism during insect development
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