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Results for “Enhancer mapping”

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At least 1,621 records · Page 90Linked to original sources
PubMed1984

Vasodilation mediated by human PTH 1-34 in the spontaneously hypertensive rat.

Parathyroid hormone's cardiovascular effects were assessed in a model of experimental hypertension with known abnormalities of calcium metabolism. Mean arterial pressure (MAP) changes and serum ionized calcium responses were measured in the spontaneously hypertensive rat (SHR) and its normotensive control, the Wistar-Kyoto (WKY), following injections of synthetic human PTH 1-34. Six 22-wk-old SHR and six WKY were given intra-arterial serial injections (0.1-100 micrograms/kg) of hPTH 1-34. Both the SHR (P less than 0.001) and WKY (P less than 0.001) demonstrated log dose-dependent hypotensive responses that were maximal at 1 min, with recovery occurring between 15 and 30 min. The slopes, however, of the dose-response curves differed (P less than 0.01). The SHR experienced a greater maximal delta MAP [-93.7 +/- 2.4 (SHR) vs. -71.2 +/- 1.6 mmHg (WKY), P less than 0.01]. Furthermore, the duration of the hypotensive action of hPTH 1-34 was significantly longer (P less than 0.001) in the SHR. Even when corrected for base-line MAP the SHR demonstrated a significant (P = 0.025) enhancement of this vasodilator response at doses of 5 micrograms/kg and greater at time intervals between 3 and 9 min after injection. A transient decrease [2.25 +/- 0.10 (pre) vs. 2.17 +/- 0.11 meq/liter (1 min post), P less than 0.01] in serum ionized calcium occurred at 1 min. We conclude that hPTH 1-34 is a potent vasoactive peptide in both the normotensive WKY and the SHR. The greater maximal hypotensive response to hPTH 1-34 and the prolongation of this cardiovascular effect in the SHR may be an additional manifestation of this experimental animal's acknowledged abnormalities of cellular membrane calcium and phospholipid metabolism.

Animals↗
PubMed2005

Transforming growth factor-beta signaling during epithelial-mesenchymal transformation: implications for embryogenesis and tumor metastasis.

The molecular mechanisms of epithelial-mesenchymal transformation (EMT) have long been studied to gain a greater understanding of this distinct change in cellular morphology. Early studies of the developing embryo have designated the involvement of Wnt signaling in EMT, through an activated complex of the lymphoid-enhancing factor-1 (LEF-1) transcription factor and the cell adhesion molecule beta-catenin. However, more recent studies have implicated a significant role of the transforming growth factor-beta (TGF-beta) in causing EMT in both development and pathology. The ability of TGF-beta isoforms to signal through a variety of molecules such as Smads, phosphatidylinositol 3-kinase (PI3K), and mitogen-activated protein kinase (MAPK) creates an incredible complexity as to their role in this transition. Here we assess the biochemical signaling pathways of TGF-beta and their potential cross-interaction with traditional Wnt signaling molecules to bring about EMT during embryogenesis and tumor metastasis.

Animals↗
PubMed2004

Cell surface-associated Tat modulates HIV-1 infection and spreading through a specific interaction with gp120 viral envelope protein.

Human immunodeficiency virus-1 (HIV-1) Tat, a nuclear transactivator of viral gene expression, has the unusual property of being released by infected cells. Recent studies suggest that extracellular Tat is partially sequestered by heparan sulfate proteoglycans. As a consequence, Tat is concentrated on the cell surface and protected from proteolytic degradation, thus remaining in a biologically active form. We show that Tat binds the surfaces of both HIV-1-infected and surrounding uninfected cells. We provide evidence for a specific interaction between Tat and the HIV-1 glycoprotein 120 (gp120) envelope protein, which enhances virus attachment and entry into cells. We map the interacting sites of both Tat and gp120 and show that synthetic peptides mimicking the gp120 site inhibit HIV-1 infection. Our data demonstrate that membrane-associated Tat is a novel modulator of virus entry and suggest that the Tat-gp120 interaction represents a critical step in HIV-1 spreading during the course of infection.

Gene Products, tat↗
PubMed2001

A novel myeloid-restricted zebrafish CCAAT/enhancer-binding protein with a potent transcriptional activation domain.

The CCAAT/enhancer-binding protein (C/EBP) family consists of transcription factors essential for hematopoiesis. The defining feature of the C/EBPs is a highly conserved carboxy-terminal bZIP domain that is necessary and sufficient for dimerization and DNA binding, whereas their amino-terminal domains are unique. This study reports a novel c/ebp gene (c/ebp1) from zebrafish that encodes a protein homologous to mammalian C/EBPs within the bZIP domain, but with an amino terminus lacking homology to any C/EBP or to any known sequence. In zebrafish embryos, c/ebp1 expression was initially observed in cells within the yolk sac circulation valley at approximately the 16-to 18-somite stage, and at 24 hours postfertilization (hpf), also in circulating cells. Most c/ebp1(+) cells also expressed a known early macrophage marker, leukocyte-specific plastin (l-plastin). Expression of both markers was lost in cloche, a mutant affecting hematopoiesis at the level of the hemangioblast. Expression of both markers was retained in m683 and spadetail, mutants affecting erythropoiesis, but not myelopoiesis. Further, c/ebp1 expression was lost in a mutant with defective myelopoiesis, but intact erythropoiesis. These data suggest that c/ebp1 is expressed exclusively in myeloid cells. In electrophoretic mobility shift assays, c/ebp1 was able to bind a C/EBP consensus DNA site. Further, a chimeric protein containing the amino-terminal domain of c/ebp1 fused to the DNA-binding domain of GAL4 induced a GAL4 reporter 4000-fold in NIH3T3 cells. These results suggest that c/ebp1 is a novel member of the C/EBP family that may function as a potent transcriptional activator in myeloid cells.

Amino Acid Sequence↗
PubMed2000

Activin/nodal responsiveness and asymmetric expression of a Xenopus nodal-related gene converge on a FAST-regulated module in intron 1.

Vertebrate Nodal-related factors play central roles in mesendoderm induction and left-right axis specification, but the mechanisms regulating their expression are largely unknown. We identify an element in Xnr1 intron 1 that is activated by activin and Vg1, autoactivated by Xnrs, and suppressed by ventral inducers like BMP4. Intron 1 contains three FAST binding sites on which FAST/Smad transcriptional complexes can assemble; these sites are differentially involved in intron 1-mediated reporter gene expression. Interference with FAST function abolishes intron 1 activity, and transcriptional activation of Xnrs by activin in embryonic tissue explant assays, identifying FAST as an essential mediator of Xnr autoregulation and/or 'signal relay' from activin-like molecules. Furthermore, the mapping of endogenous activators of the Xnr1 intronic enhancer within Xenopus embryos agrees well with the pattern of Xnr1 transcription during embryogenesis. In transgenic mice, Xnr1 intron 1 mimics a similarly located enhancer in the mouse nodal gene, and directs FAST site-dependent expression in the primitive streak during gastrulation, and unilateral expression during early somitogenesis. The FAST cassette is similar in an ascidian nodal-related gene, suggesting an ancient origin for this regulatory module. Thus, an evolutionarily conserved intronic enhancer in Xnr1 is involved in both mesendoderm induction and asymmetric expression during left-right axis formation.

Activins↗
PubMed2003

Surface-enhanced resonance raman scattering: single-molecule detection in a Langmuir-Blodgett monolayer.

Surface-enhanced resonance Raman scattering (SERRS) is used for single-molecule detection from spatially resolved 1-microm2 sections of a Langmuir-Blodgett (LB) monolayer deposited onto a Ag film. The target molecule, bis (benzimidazo) thioperylene (BZP), is dispersed in an arachidic acid monomolecular layer containing one BZP molecule per microm2, which is also the probing area of the Raman microscope. For concentrated samples (attomole quantities in the field of view), average SERRS, surface-enhanced fluorescence (SEF), and Raman imaging, including line mapping and global images at different temperatures, were recorded. Single-molecule SERRS spectra, obtained using an LB monolayer, present changes in bandwidth and relative intensities, highlighting the properties of single-molecule SERRS that are lost in average SERRS measurements of mixed LB monolayers obtained at the same temperatures. Also, the dilute system phenomenon of blinking is discussed with regard to results obtained from LB monolayers. The dilution process used in the single-molecule LB SERRS work is independently supported by fluorescence results obtained from very dilute solutions with monomer concentrations down to 10(-12) M.

Benzimidazoles↗
PubMed2005

Panax notoginseng supplementation enhances physical performance during endurance exercise.

The purpose of this study was to investigate whether a single 1,350-mg dose of Panax notoginseng (PNG) could enhance aerobic capacity, endurance, and mean blood pressure (MAP) in young adults. We randomly assigned 29 untrained adults, aged 20-35 years, to an experimental (EXP, n = 13) or a control (CON, n = 16) group. For 30 days, the EXP took 1,350 mg per day of PNG capsule and the CON consumed 1,350 mg per day of starch capsule. Measurement variables were taken before and after 30 days of either PNG supplement or placebo. Results show that the EXP improved (p < 0.05) their endurance time by >7 minutes, and lowered (p < 0.05) maximal MAP (from 113 +/- 12 to 109 +/- 14 mm Hg) and Vo2 at the 24th minute (from 32.5 +/- 8 to 27.6 +/- 8 ml.kg-1.min-1) during endurance cycle exercise. Based on this study, we conclude that 1,350 mg per day PNG supplement for 30 days improved endurance time to exhaustion, and lowered MAP and Vo2 during endurance exercise.

Adult↗
PubMed2002

Direct effects of ciliary neurotrophic factor on brown adipocytes: evidence for a role in peripheral regulation of energy homeostasis.

Ciliary neurotrophic factor (CNTF) plays an important role in regulating neuronal growth. Recently, central anorexigenic effects of this cytokine have been characterized. However, peripheral effects on tissues that actively contribute to the regulation of energy homeostasis have not been described. Here, we report direct potent and selective effects of CNTF on growth factor and metabolic signalling intermediates in mouse brown adipocytes. CNTF stimulates STAT3, MAP kinase, Akt, and p70 S6 kinase. We find that, next to mediating Akt and p70 S6 kinase activation, both phosphatidylinositol 3-kinase and protein kinase C are separately acting, main intermediates for inducing mitogen-activated protein (MAP) kinase activation. On a functional level, CNTF enhances beta3-adrenergic induction of uncoupling protein-1. Thus, these results demonstrate direct effects of CNTF on adipose tissue signalling and metabolism and suggest a novel role for this cytokine in the peripheral regulation of energy homeostasis.

Adipocytes↗
PubMed2003

The molecular and cellular basis of corticosteroid resistance.

Corticosteroids (CS) can modulate gene expression and are often used to treat a range of immunological and inflammatory diseases such as asthma, inflammatory bowel disease and rheumatoid arthritis. However, a proportion of patients fail to show an adequate response. On this basis patients have been subdivided into CS-sensitive (SS) and -resistant (SR) subgroups. The ability of CS to inhibit peripheral blood T cell proliferation in vitro has also been used similarly. In rheumatoid arthritis (RA), the in vitro-defined SS and SR subgroups correlate with the clinical responses to CS therapy. The mechanisms responsible for this observation are unknown but they appear to involve a number of known molecular events related to the described mechanisms of action of CS. These include alterations in the functional status of CS receptor-alpha, perturbations of the cytokine and hormonal milieu and intracellular signalling pathways. Peripheral blood mononuclear cells (MNCs) from SR significantly overexpress activated NF-kappaB. In vitro, CS fail to significantly inhibit concanavalin A (conA)-induced NF-kappaB activation in MNCs from SR RA patients. The alterations in the intracellular signalling pathways may explain in part our observations seen in SR RA subjects, CS fail to significantly inhibit conA-induced interleukin (IL)-2 and IL-4 secretion and lipopolysaccharide-induced IL-8 and IL-1beta secretion in vitro. CS therapy fails to reduce the circulating levels of IL-8 and IL-1beta in RA patients. In asthma, CS fail to induce L10 in SR asthma patients. Other molecular mechanisms such as enhanced AP-1 expression and alterations in the MAP kinase pathway are most likely to be involved too and we are currently investigating such possibilities. A full understanding of the molecular basis of SR will lead to the development of more rational therapeutic strategies.

Adrenal Cortex Hormones↗
PubMed2001

Identification of C15orf5, a heart-enriched transcript on chromosome 15q23-q24.

We have isolated C15orf5, a novel human gene lacking homology to any known protein. The C15orf5 gene encodes a transcript of 1,519 nt with an ORF of 94 amino acids and a predicted protein size of 11.5 kDa. Northern blot analysis showed enhanced expression of C15orf5 in heart. C15orf5 was mapped to chromosome 15q23-q24 using the Stanford TNG4 Radiation Hybrid panel.

Base Sequence↗
PubMed2000

A novel human multiple myeloma-derived cell line, NCU-MM-1, carrying t(2;11)(q11;q23) and t(8;22)(q24;q11) chromosomal translocations with overexpression of c-Myc protein.

A novel cell line, designated as NCU-MM-1, was established from a 66-year-old female patient with multiple myeloma (MM) that had shown rapid progression from solitary plasmacytoma to plasma cell leukemia. Interestingly, cytogenetic analysis including fluorescence in situ hybridization analysis disclosed that this cell line carried 2 kinds of chromosomal translocations involving immunoglobulin light chain (IgL) gene loci without the presence of 14q32 translocations (14q+). The Ig lambda locus juxtaposed to the c-MYC locus at 8q24 on the derivative (8) chromosome and a concomitant overexpression of the c-Myc protein was observed. On the derivative (11) chromosome, the Ig kappa locus was also fused to the chromosome 11q23 locus, which is known to be a nonrandom translocation breakpoint in mature B-cell malignancies. The NCU-MM-1 cell line may thus be useful not only for the identification of the responsible proto-oncogene(s) mapped to 11q23, deregulated by the Ig kappa enhancer sequences, but also for clarification of the molecular origin of MM lacking 14q+ chromosomes because IgL rearrangements can physiologically begin to occur in the pre-B-cell stage.

Aged↗
PubMed2002

Imaging-based integrative models of the heart: closing the loop between experiment and simulation.

We describe methodologies for: (a) mapping ventricular activation using high-density epicardial electrode arrays; (b) measuring and modelling ventricular geometry and fibre orientation at high spatial resolution using diffusion tensor magnetic resonance imaging (DTMRI); and (c) simulating electrical conduction; using comprehensive data sets collected from individual canine hearts. We demonstrate that computational models based on these experimental data sets yield reasonably accurate reproduction of measured epicardial activation patterns. We believe this ability to electrically map and model individual hearts will lead to enhanced understanding of the relationship between anatomical structure, and electrical conduction in the cardiac ventricles.

Algorithms↗
PubMed1992

Effect of captopril and the nonpeptide angiotensin II antagonists, SK&F 108566 and EXP3174, on renal function in dogs with a renal artery stenosis.

Treatment with an angiotensin converting enzyme (ACE) inhibitor can result in acute renal failure in patients with a renal artery stenosis. In the present study the effects of the selective nonpeptide angiotensin II antagonists, SK&F 108566 ((E)-alpha-[[2-Butyl-1-[(4-carboxyphenyl)methyl]-1H-imidazol-5-yl] methylene]-2-thiophenepropanoic acid) and EXP3174 (2-n-Butyl-4-chloro-1-[(2'-(1H-tetrazol-5-yl)-biphenyl-4-yl) methyl]imidazole-5-carboxylic acid hydrochloride) (the active metabolite of DuP 753, losartan) were compared with the ACE inhibitor, captopril, in the anesthetized dog which had been uninephrectomized and the remaining renal artery clamped to reduce renal blood flow (RBF) by approximately 50%. All three agents resulted in dose-dependent reductions in mean arterial pressure (MAP), glomerular filtration rate (GFR) and RBF. The maximum responses to captopril and SK&F 108566 were similar with MAP, RBF and GFR all decreasing approximately 30%. EXP3174 also resulted in decreases in GFR and RBF of approximately 30%; however, there was a smaller (approximately 17%) decrease in MAP. The data indicate that the possible bradykinin enhancing activity of ACE inhibitors may not provide any moderating activity of ACE inhibitor-induced reduction in GFR observed in dogs with a renal artery stenosis.

Acrylates↗
PubMed2004

Identification and characterization of human FOXK1 gene in silico.

Forkhead-box (FOX) family transcription factors are implicated in carcinogenesis and embryogenesis. Here, we identified and characterized the human FOXK1 gene by using bioinformatics. Complete coding sequence of human FOXK1 cDNA was determined by assembling CB959941 EST, AW206906 EST, and 5'-truncated FLJ16099 (AK122663.1) cDNA. FOXK1 gene, consisting of nine exons, was mapped to human chromosome 7p22.1. Mouse Foxk1 (NM_199068.1) was an aberrant cDNA with frame shifts due to multiple insertions and deletions, while mouse IMAGE6853263 (BC060238.1) was a Foxk1 cDNA with a frame shift due to two base deletions. Complete coding sequence of mouse Foxk1 cDNA was determined by inserting CA nucleotides between nucleotide position 1628 and 1629 of BC060238.1. Foxk1 gene, consisting of nine exons, was mapped to mouse chromosome 5G2. Because interleukin enhancer-binding factor 1 (ILF1) gene at human chromosome 17q25.3 was the paralog of FOXK1 gene, ILF1 gene was designated the FOXK2 gene. Xenopus BC046369.1 cDNA was Foxk2 ortholog rather than Foxk1 ortholog. Human FOXK1 (733 aa) showed 88.7% total amino-acid identity with mouse Foxk1 (719 aa), 48.7% total amino-acid identity with human FOXK2, and 47.5% total amino-acid identity with Xenopus Foxk2. Forkhead associated (FHA) domain and FOX domain were conserved among human FOXK1, FOXK2, mouse FoxK1, and Xenopus Foxk2. At least 42 FOX family genes, including FOXK1, FOXN5 (FOXR1) and FOXN6 (FOXR2), have been identified within the human genome.

Amino Acid Sequence↗
PubMedDate not supplied

[Spatial organization of the chicken alpha-globin gene domain in cells of different].

We have developed a technique for mapping the sites of DNA attachment to the nuclear matrix by hybridization of nuclear matrix DNA with an oligonucleotide array. The latter was made by immobilization of 60-mer oligonucleotides distributed within the area under study with a 2 Kb step on nylon filter. Using this approach we have analyzed the mode of interaction of a 100 Kb fragment of chicken chromosome 16 including the alpha-globin gene domain with the nuclear matrix. The 40 Kb DNA loop including all alpha-globin genes was detected in erythroid cells. One of the borders of this loop colocalized with the previously mapped MAR element and CTCF-dependent enhancer-blocking element. Also, a long transcribed area was found to be preferentially associated with the nuclear matrix. The spatial organization of the area under study in lymphoid cells was drastically different from this observed in erythroid cells.

Animals↗
PubMed2006

Interpreting change scores of tests and measures used in physical therapy.

Over the past decade, the methods and science used to describe changes in outcomes of physical therapy services have become more refined. Recently, emphasis has been placed not only on changes beyond expected measurement error, but also on the identification of changes that make a real difference in the lives of patients and families. This article will highlight a case example of how to determine and interpret "clinically significant change" from both of these perspectives. The authors also examine how to use item maps within an item response theory model to enhance the interpretation of change at a content level. Recommendations are provided for physical therapists who are interpreting changes in the context of clinical practice, case reports, and intervention research. These recommendations include a greater application of indexes that help interpret the meaning of clinically significant change to multiple clinical, research, consumer, and payer communities.

Child↗