177,511 research outputs found
Expression of cell-cycle-dependent genes in phytohemagglutinin-stimulated human lymphocytes.
No full textWe have investigated the expression of certain cell-cycle-dependent genes in human peripheral blood mononuclear cells (PBMC) stimulated by phytohemagglutinin (PHA). The genes studied had been previously identified as cell-cycle dependent in other cell types from different species and were induced by different mitogens. One of these genes (2F1) and the gene for the interleukin 2 receptor were induced by PHA even in cultures partially depleted of accessory cells where the lymphocytes grew in size but failed to enter S phase. The other genes (c-myc, 4F1, JE-3, and KC-1) were induced only in complete cultures of PBMC stimulated by PHA. These results confirm the dissociation between growth in size and cell DNA replication that can occur during cell-cycle progression. Moreover, the time course of appearance of detectable levels of RNA for these genes suggests that they may be used as markers of cell-cycle progression in the transition of lymphocytes from G0 to S phase
Effect of interleukin-2 on the expression of cell cycle genes in human T lymphocytes.
No full textWe have studied the expression of seven cell cycle-dependent genes in phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells, in macrophage-depleted cultures and in macrophage-depleted cultures plus Interleukin-2 (IL-2). The expression of all seven genes is increased in PHA stimulated peripheral cells. Only two (2F1 and the IL-2 receptor) are increased in PHA-stimulated macrophage depleted cultures. Addition of IL-2 to these cultures increased the RNA levels of four genes (KC-1, c-myc, beta-actin and IL-2R), but has no effect on three others (4F1, 2F1, and JE-3). The results indicate that the expression of these cell cycle genes is regulated by different components of the mitogenic stimulus
Altered mRNA translation: possible mechanism for CML disease progression.
No full textChronic myelogenous leukemia (CML) is a clonal disorder arising from neoplastictransformation of the hematopoietic stem cell.1 The typical clinical course of CMLinvolves progression from a protracted chronic phase (CP) to a rapidly fatal blast crisis(BC) characterized by clonal expansion of an immature population of myeloid blast cellswhich exhibit enhanced proliferative potential, reduced susceptibility to apoptosis, anddifferentiation arrest. The latter feature is typical of CML-BC as apparently normalneutrophils and late myeloid precursors accumulate in the bone marrow and peripheralblood of CML-chronic phase patients.1,2 The introduction of the Abl kinase inhibitorGleevec (imatinib mesylate or STI571) as the drug of choice in the treatment of CML islikely to have a profound effect on the course of chronic phase CML. However, in blastcrisis CML, the therapeutic effect of Gleevec is transient and relapse of the disease is themost frequent outcome.3 Thus, it remains critically important to understand the molecularmechanisms underlying progression of CML from chronic phase to blast crisis, as thisadvanced disease stage does not respond to conventional therapy and is associated with ahigh mortality rate.While there is no doubt that expression of the BCR/ABL oncoprotein in hematopoieticstem cells is the initiating event in CML, it is somewhat controversial whether BCR/ABLplays an equally essential role during disease progression or in the blast crisis disease stage.In growth factor-dependent cell lines, ectopic expression of the BCR/ABL oncoproteinis sufficient to induce factor-independent proliferation, increased survival, and differentiationarrest, a phenotype reminiscent of that of CML blast crisis cells.4,5 However, constitutiveexpression of BCR/ABL in normal primary marrow cells leads to a myeloproliferativedisorder which is, instead, reminiscent of chronic phase CML.6 Thus, it is unclear whetherBCR/ABL oncogenic activity per se accounts for CML disease progression or if secondarygenetic alterations are required. In any case, continuous expression/activity of BCR/ABLis necessary for maintaining the leukemic phenotype in mice.7,8There is evidence that genetic inactivation of p53 occurs in blast crisis CML. Althougha p53-deficient background appears to favor blastic transformation in the appropriatemouse models,9,10 mutations in the p53 gene have been detected only in the 25% of blastcrisis.11 Another recurrent mutation in blast crisis CML is the double Philadelphiachromosome, which is detected in 20% of cases.12 In addition, expression of BCR/ABLis higher in mononuclear cells from blast crisis compared to chronic phase CMLpatients,13 and growth factor-independent and differentiation-arrested cell lines expressinghigh doses of BCR/ABL develop from growth factor-dependent cells that express low levelsof the p210 BCR/ABL oncoprotein.14 Thus, high levels of BCR/ABL in the appropriatetarget cells may have a role in blastic transformation. Consistent with this, the increasedexpression of BCR/ABL during disease progression and transformation of growth factor-dependent myeloid precursor cell lines correlates with changes in gene expression, some ofwhich involve regulators of mRNA metabolism like FUS, hnRNP A1, hnRNP E2 andLa.5,14-16In particular, the increased expression of hnRNP E2 and La, two shuttling RNA bindingproteins which function as regulators of mRNA translation,17,18 suggests that BCR/ABLand, perhaps, other oncogenic tyrosine kinases, may modulate gene expression at thetranslational level
Modeling of Variable Valve Timing on High Performance Engine using Power-Oriented Graphs Method
No full textEngine efficiency is one of the key aspects to reduce CO2 emissions. In order to improve the emission maintaining high performance capabilities several devices are introduced in the system; variable valve timing technology allows more flexibility for modern engines to meet peak performance, fuel economy and low emissions targets [7] while providing good driveability. This paper describes the Lamborghini continuously-variable cam phaser model using a graphical technique, called Power Oriented Graphs (POG), this uses an energetic approach for representing the physical systems. The generally accepted approach is to calibrate an engine on a dynamometer and to adjust the operation of the engine to meet performance targets. With the current build and test approach, these adjustments may not be made until well into the development program, and this calibration is a costly and time consuming step in the engine development process: the main purpose of this works is showing how was described the model in order to get more easy and fast the calibrating operations. Furthermore the usefulness to model the system consists of analyzing in simulation many more system configurations than those available for real experiments so it's important using a simple methodology that is able to analyze the whole system's dynamic in order to reach the performance expectations. The results obtained were validated demonstrating the effectiveness of the POG technique. Copyright © 2011 SAE International
Representations of celestial coordinates in FITS
No full textIn Paper I, Greisen & Calabretta ([CITE]) describe a generalized
method for assigning physical coordinates to FITS image pixels. This paper
implements this method for all spherical map projections likely to be of
interest in astronomy. The new methods encompass existing informal FITS
spherical coordinate conventions and translations from them are described.
Detailed examples of header interpretation and construction are given
A cell proliferation-dependent multiprotein complex NC-3A positively regulates the CD34 promoter via a TCATTT-containing element.
No full textThe CD34 cell surface antigen is a glycoprotein expressed by hematopoietic stem and progenitor cells and also by certain nonhematopoietic cell-types. Because CD34 expression is regulated both at the transcriptional and the posttranscriptional level, we attempted to identify factors that, by interacting with the 5' flanking region of the human CD34 gene, may regulate its promoter activity in proliferating hematopoietic cells. By electrophoretic mobility shift assay, UV cross-linking and DNase I footprinting analyses, we identified a multiprotein complex, designated NC-3A, that specifically interacts with the CD34 promoter region from nucleotides -375 to -351. Sequence analysis of this region revealed the presence of a distinct motif, TCATTT. Chloramphenicol acetyl-transferase assays used to assess promoter activity in transiently transfected cells showed that this TCATTT-containing element, which is conserved in both the human and the murine CD34 genes, mediates positive regulatory activity in hematopoietic and nonhematopoietic cells, and acts as an enhancer when placed upstream of a heterologous promoter. Moreover, loss of CD34 promoter activity was caused by mutation of the TCATTT motif. In addition, the interaction of the nuclear multiprotein complex NC-3A with this enhancer element is proliferation-dependent. These data indicate that, although not cell-type specific, the formation of a multiprotein complex NC-3A interacting with the region from nucleotides -375 to 351 plays an important role in controlling CD34 promoter activity in proliferating hematopoietic cells
Appropriate Similarity Measures for Author Cocitation Analysis
No full textWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Ligand binding to Fc gamma R induces c-myc-dependent apoptosis in IL-2-stimulated NK cells.
No full textThe role of signals transduced via Fc gamma RIIIA in the modulation of the proliferative potential of NK cells has been investigated. Fc gamma R stimulation does not induce NK cell proliferation, and inhibits that induced by IL-2, but not by IL-12, as measured by [3H]TdR incorporation, without affecting entrance or progression through cell cycle. The inhibitory effect depends, at least in part, on induced apoptosis of the cells, detected by both light and electron microscopy examination. Fc gamma R stimulation induces apoptosis only in NK cells that have been previously activated by IL-2: this occurs within 3 h from receptor stimulation and is independent from de novo receptor-induced RNA or protein synthesis, but requires receptor-induced activation of protein tyrosine kinases and extracellular Ca2+ influx. IL-2 induces accumulation of c-myc mRNA in NK cells, and treatment of the cells with c-myc antisense oligodeoxyribonucleotides during the IL-2 stimulation phase inhibits the susceptibility to Fc gamma RIIIA-induced cell death, indicating that the induction of sustained levels of this proto-oncogene is necessary for the phenomenon. Thus, a two-step model is suggested for the Fc gamma R-induced apoptosis in IL-2 activated NK cells: the first step involves induced expression of c-myc, and possibly other permissive factors, upon IL-2 prestimulation; the second depends directly on the stimulation of the receptor, independently of additional gene induction. The evidence presented here suggests a mechanism of control of NK cell expansion at the latest stages of Ab-dependent immune responses
Representations of spectral coordinates in FITS
No full textGreisen & Calabretta (2002, A&A, 395, 1061) describe a generalized
method for specifying the coordinates of FITS data samples. Following
that general method, Calabretta & Greisen (2002, A&A, 395, 1077) describe
detailed conventions for defining celestial coordinates as they are
projected onto a two-dimensional plane. The present paper extends the
discussion to the spectral coordinates of wavelength, frequency, and
velocity. World coordinate functions are defined for spectral axes
sampled linearly in wavelength, frequency, or velocity, linearly in
the logarithm of wavelength or frequency, as projected by ideal
dispersing elements, and as specified by a lookup table
The Jun family members, c-Jun and JunD, transactivate the human c-myb promoter via an Ap1-like element.
No full textThe c-myb protooncogene, which is preferentially expressed in hematopoietic cells at the G1/S boundary of the cell cycle, encodes a transcriptional activator that functions via DNA binding. The regulatory mechanisms governing this specific pattern of expression are not fully understood, although human c-myb expression appears to be positively autoregulated via myb-binding sites in the 5'-flanking region of the c-myb gene (Nicolaides, N. C., Gualdi, R., Casadevall, C., Manzella, L., and Calabretta, B. (1991) Mol. Cell. Biol. 11, 6166-6176). To determine the contribution of other transcription regulators such as JUN family members in the control of c-myb expression, transient expression assays were carried out which revealed a 6- to a 15-fold enhancement by c-Jun and JunD, but not JunB, in chloramphenicol acetyltransferase reporter gene expression driven by different segments of the human c-myb 5'-flanking region. An Ap1-like element located at nucleotide -149 from the c-myb initiation site appears to be required for this transactivation upon binding to a nuclear protein complex containing c-Jun and JunD, since site-directed mutations of this Ap1-like element abolished c-Jun and JunD binding and transactivation. Exposure of phytohemagglutinin-stimulated peripheral blood mononuclear cells to c-jun and junD antisense oligodeoxynucleotides resulted in a 46 and 43% inhibition of T-lymphocyte proliferation that was accompanied by a decrease in c-myb mRNA levels as compared with sense-treated cultures. Because T-lymphocytes induced to proliferate express c-jun and junD before c-myb, these data suggest a mechanism whereby c-Jun and JunD contribute to the transcriptional activation of c-myb that, in turn, is maintained at the G1/S transition and during S phase by positive autoregulation
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