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A novel human CD4(+) T-cell inducer subset with potent immunostimulatory properties

NDHLOVU, Lishomwa C.; LEAL, Fabio E.; ECCLES-JAMES, Ijeoma G.; JHA, Aashish R.; LANTERI, Marion; NORRIS, Philip J.; BARBOUR, Jason D.; WACHTER, Douglas J.; ANDERSSON, Jan; TASKEN, Kjetil; TORHEIM, Eirik A.; AANDAHL, Einar M.; KALLAS, Esper G.; NIXON, Doug
Fonte: WILEY-V C H VERLAG GMBH Publicador: WILEY-V C H VERLAG GMBH
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
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The complexity of immunoregulation has focused attention on the CD4(+) T ""suppressor"" regulatory cell (T(reg)), which helps maintain balance between immunity and tolerance. An immunoregulatory T-cell population that upon activation amplifies cellular immune responses was described in murine models more than 30 years ago; however, no study has yet identified a naturally occurring T ""inducer"" cell type. Here, we report that the ectoenzyme CD39/NTPDase1 (ecto-nucleoside triphosphate diphosphohydrolase 1) helps to delineate a novel population of human ""inducer"" CD4(+) T cells (T(ind)) that significantly increases the proliferation and cytokine production of responder T cells in a dose-dependent manner. Furthermore, this unique T(ind) subset produces a distinct repertoire of cytokines in comparison to the other CD4(+) T-cell subsets. We propose that this novel CD4(+) T-cell population counterbalances the suppressive activity of suppressor T(reg) in peripheral blood and serves as a calibrator of immunoregulation.; National Institutes of Health (NIH), University of California, San Francisco-Gladstone Institute of Virology & Immunology Center[P30 AI027763]; National Institutes of Health (NIH), University of California, San Francisco-Gladstone Institute of Virology & Immunology Center[AI060379]; National Institutes of Health (NIH)...

Interaction of Gal repressor with inducer and operator: Induction of gal transcription from repressor-bound DNA

Chatterjee, Sumana; Zhou, Yan-Ning; Roy, Siddhartha; Adhya, Sankar
Fonte: The National Academy of Sciences of the USA Publicador: The National Academy of Sciences of the USA
Tipo: Artigo de Revista Científica
Publicado em 01/04/1997 EN
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27.04%
Gal repressor inhibits transcription from the gal promoter (P1) when it binds to the cognate operator (OE). The repression is relieved by the presence of the inducer d-galactose. Compared with its interaction with free repressor, d-galactose binds to the repressor–operator complex with 10-fold reduced affinity as determined by fluorescence enhancement measurements. Thermodynamic analysis and fluorescence anisotropy showed that the stability of the repressor–operator complex is reduced by only 7-fold by the presence of the inducer in the complex. The formation of the inducer–repressor–operator ternary complex has been confirmed by CD spectral analysis. Fluorescence spectroscopy and energy transfer experiments suggest that individual allosteric effects of the two ligands, inducer and operator, on Gal repressor are responsible for the slightly weakened stability of the ternary complex compared with the stability of the inducer–repressor and repressor–operator complexes. In vitro transcription results demonstrated full derepression of transcription of the P1 promoter under conditions in which the concentrations of the inducer–repressor binary complex are severalfold higher than the dissociation constant of the inducer–repressor–operator ternary complex into inducer–repressor and free DNA. These results strongly suggest that the inducer binding to the repressor–operator complex does not lead to dissociation of the repressor from the operator during transcription induction. Because Gal repressor inhibits transcription by modulating the α subunit of the P1-bound RNA polymerase...

A major inducer of anticarcinogenic protective enzymes from broccoli: isolation and elucidation of structure.

Zhang, Y; Talalay, P; Cho, C G; Posner, G H
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 15/03/1992 EN
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26.89%
Consumption of vegetables, especially crucifers, reduces the risk of developing cancer. Although the mechanisms of this protection are unclear, feeding of vegetables induces enzymes of xenobiotic metabolism and thereby accelerates the metabolic disposal of xenobiotics. Induction of phase II detoxication enzymes, such as quinone reductase [NAD(P)H:(quinone-acceptor) oxidoreductase, EC 1.6.99.2] and glutathione S-transferases (EC 2.5.1.18) in rodent tissues affords protection against carcinogens and other toxic electrophiles. To determine whether enzyme induction is responsible for the protective properties of vegetables in humans requires isolation of enzyme inducers from these sources. By monitoring quinone reductase induction in cultured murine hepatoma cells as the biological assay, we have isolated and identified (-)-1-isothiocyanato-(4R)-(methylsulfinyl)butane [CH3-SO-(CH2)4-NCS, sulforaphane] as a major and very potent phase II enzyme inducer in SAGA broccoli (Brassica oleracea italica). Sulforaphane is a monofunctional inducer, like other anticarcinogenic isothiocyanates, and induces phase II enzymes selectively without the induction of aryl hydrocarbon receptor-dependent cytochromes P-450 (phase I enzymes). To elucidate the structural features responsible for the high inducer potency of sulforaphane...

Bordetella Interspecies Allelic Variation in AlcR Inducer Requirements: Identification of a Critical Determinant of AlcR Inducer Responsiveness and Construction of an alcR(Con) Mutant Allele

Brickman, Timothy J.; Armstrong, Sandra K.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /03/2002 EN
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26.97%
Previous studies established the critical roles of AlcR and alcaligin inducer in positive regulation of alcaligin siderophore biosynthesis and transport genes in Bordetella pertussis and Bordetella bronchiseptica. Transcriptional analyses using plasmid-borne alcR genes of B. pertussis UT25 and B. bronchiseptica B013N to complement the alcR defect of B. bronchiseptica strain BRM13 (ΔalcR1 alcA::mini-Tn5 lacZ1) revealed interspecies differences in AlcR inducer requirements for activation of alcABCDER operon transcription. Whereas the B. pertussis UT25 AlcR protein retained strong inducer dependence when produced from multicopy plasmids, B. bronchiseptica B013N alcR partially suppressed the alcaligin requirement for transcriptional activation. Functional analysis of AlcR chimeras produced by interspecies domain swapping and interspecies reciprocal site-specific mutagenesis determined that the phenotypic difference in AlcR inducer dependence was due to a single amino acid difference within the proposed inducer-binding and multimerization domain of AlcR. Structural predictions guided the design of a mutant AlcR protein with a single amino acid substitution at this critical position, AlcR(S103T), that was fully constitutive not only when produced from multicopy plasmids but also at a single-copy gene dosage. These results indicate that AlcR residue 103 affects a critical determinant of alcaligin inducer dependence of AlcR-mediated transcriptional activation. The alcR(S103T) mutant allele is the first alcR(Con) mutant allele identified.

INDUCTION OF STAPHYLOCOCCAL PENICILLINASE BY BENZYLPENICILLIN: EFFECT OF pH, CONCENTRATION OF FERROUS ION AND INDUCER, AND DURATION OF EXPOSURE OF CELLS TO INDUCER

Leitner, Felix; Sweeney, Helen M.; Martin, T. F.; Cohen, Sidney
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /10/1963 EN
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26.94%
Leitner, Felix (Michael Reese Hospital and Medical Center, Chicago, Ill.), Helen M. Sweeney, T. F. Martin, and Sidney Cohen. Induction of staphylococcal penicillinase by benzylpenicillin: effect of pH, concentration of ferrous ion and inducer, and duration of exposure of cells to inducer. J. Bacteriol. 86:717–727. 1963.—The kinetics of induction of penicillinase by benzylpenicillin in exponentially multiplying Staphylococcus aureus strain 55-C-1 were shown to vary with the pH. At pH 7.3 in the absence of free inducer, the rate of increase of penicillinase activity rapidly declined and came to a halt. At pH 5.4 to 5.5 and in the presence of optimal concentrations of Fe++, the penicillinase activity of the induced culture increased linearly with time for 2.5 or more generations, but the rate of increase usually declined eventually. Evidence was advanced to support the concept that the acidic pH and optimal Fe++ concentration maintain the induced formation of enzyme. The induced increase in penicillinase activity appeared 3 to 4 min after the addition of benzylpenicillin. The degree of induction of penicillinase varied with the duration of exposure of the staphylococci to the inducer and with the concentration of inducer. Maximal induction under our conditions was attained by exposure for 15 min to benzyl-penicillin at an initial concentration between 0.6 and 2 units/ml.

Inducer-mediated commitment of murine erythroleukemia cells to differentiation: a multistep process.

Chen, Z; Banks, J; Rifkind, R A; Marks, P A
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /01/1982 EN
Relevância na Pesquisa
26.89%
There are a number of agents which, when added to cultures of murine erythroleukemia cells (MELC), markedly increase the probability of commitment to express the characteristics of terminal erythroid differentiation, including loss of proliferative capacity and increased accumulation of globin mRNA and hemoglobin. Some characteristics of inducer-mediated commitment of MELC to terminal erythroid differentiation were examined by determining the effects of dexamethasone (an inhibitor of inducer-mediated MELC differentiation) and of hemin (an inducer of globin mRNA accumulation). Previously, it was shown that exposure of MELC to hexamethylene-bisacetamide (HMBA) leads to commitment, detectable within 12 hr. MELC cultured with both HMBA and dexamethasone do not express commitment. MELC transferred from culture with HMBA and dexamethasone to cloning medium without these agents express commitment to terminal erythroid differentiation, indicating that MELC retain a "memory" for some early HMBA-mediated changes leading to commitment which occur even in the presence of the inhibitory steroid. The kinetics of commitment in experiments in which exposure to HMBA is interrupted, or dexamethasone is added to the culture in HMBA, suggest that there is a rate-limiting step early in the commitment process. The memory for this step persists for more than one cell cycle. Addition of hemin to cultures with HMBA and dexamethasone initiated accumulation of globin mRNA but does not reverse the steroid-mediated inhibition of terminal cell division (that is...

Non-Mendelian Female Sterility in DROSOPHILA MELANOGASTER: Characterization of the Noninducer Chromosomes of Inducer Strains

Picard, Georges; Pelisson, Alain
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /03/1979 EN
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26.97%
In relation to non-Mendelian female sterility, Drosophila melanogaster strains can be divided into two main classes, inducer and reactive. The genetic element responsible for the inducer condition (I factor) is chromosomal and may be linked to any inducer-strain chromosome. Each chromosome carrying the I factor (i+ chromosome) can, when introduced by the paternal gamete into a reactive oocyte, give rise to females (denoted SF) showing more-or-less reduced fertility. As long as i+ chromosomes are transmitted through heterozygous males with reactive originating chromosomes (r chromosomes), I factor follows Mendelian segregation patterns. In contrast, in heterozygous i+/r females, a varying proportion of r chromosomes may irreversibly acquire I factor, independently of classical genetic recombination, by a process called chromosomal contamination. The contaminated reactive chromosomes behave as i+ chromosomes.—In the present paper, evidence is given that the Luminy inducer strain displays a polymorphism for two kinds of second chromosomes. Some of them are i+, while others, denoted io, are unable to induce any SF sterility when introduced by paternal gametes into reactive oocytes. They are also unable to induce contamination of r chromosomes...

T cell development. Precursors and inducer requirements of helper effector and feedback suppression inducer cell sets

Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 01/09/1981 EN
Relevância na Pesquisa
26.94%
The surface phenotypes and differentiative history of specific helper- effector (HE) and specific feedback suppression-inducer (FBSI) cell sets were further defined in reference to the Qa-1 and I-J marker systems by culture of selected sets of cortisone-resistant nylon- purified thymocytes with antigen on primed macrophages. The generation of Ly-1:HE and Ly-1:FBSI cell sets required, in each case, two initiating sets: a precursor set and a differentiation-inducing set. Precursor sets were distinguished from inducer sets by genetic markers. Accordingly, HE cells, phenotype Ly-1:Qa-1-:I-J-, differentiated from Ly-123:Qa-1- cells in the presence of Ly-1:Qa-1+:I-J+ inducer cells; and FBSI cells, phenotype Ly-1:Qa-1+:I-J+, differentiated from Ly- 123:Qa-1- in the presence of Ly-1:Qa-1+:I-J+ inducer cells. The Ly- 123:Qa-1-precursors of HE and FBSI cells have been distinguished from one another previously but there is as yet no evidence whether differentiation of these precursor sets requires the same or different Ly-1:Qa-1+:I-J+ inducer sets.

Lysis of inducer T cell clones by activated macrophages and macrophage- like cell lines

Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 01/10/1983 EN
Relevância na Pesquisa
26.89%
We describe a sequence of reciprocal interactions between cloned inducer T cells and antigen-presenting cells (APC) that results in selective depletion of the antigen-reactive inducer cells. We show that corecognition of antigen and I-A by hapten-reactive inducer T cell clones results in (a) release of macrophage-activating factor (MAF) and other lymphokines, (b) expression of lytic activity by a subset of MAF- sensitized APC after triggering, and (3) lysis (mediated by the activated and triggered macrophage) of the inducer T cell clone and other cells in the vicinity. We suggest that this sequence of steps may limit the extent of macrophage-mediated tissue destruction by depleting the specific inducer T cell clones that initiate the response.

Flexibility in the Inducer Binding Region is Crucial for Allostery in the Escherichia coli Lactose Repressor†

Xu, Jia; Matthews, Kathleen S.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 09/06/2009 EN
Relevância na Pesquisa
27%
Lactose repressor protein (LacI) utilizes an allosteric mechanism to regulate transcription in E. coli, and the transition between inducer- and operator-bound states has been simulated by targeted molecular dynamics (TMD). The side chains of amino acids 149 and 193 interact and were predicted by TMD simulation to play a critical role in the early stages of the LacI conformational change. D149 contacts IPTG directly, and variations at this site provide the opportunity to dissect its role in inducer binding and signal transduction. Single mutants at D149 or S193 exhibit minimal change in operator binding, and alterations in inducer binding parallel changes in operator release, indicating normal allosteric response. The observation that the double mutant D149A/S193A exhibits wild-type properties excludes the requirement for inter-residue hydrogen bond formation in the allosteric response. The double mutant D149C/S193C purified from cell extracts shows decreased sensitivity to inducer binding, while retaining wild-type binding affinities and kinetic constants for both operator and inducer. By manipulating cysteine oxidation, we show that the more reduced state of D149C/S193C responds to inducer more similarly to wild-type protein, whereas the more oxidized state displays diminished inducer sensitivity. These features of D149C/S193C indicate that the novel disulfide bond formed in this mutant impedes the allosteric transition...

Spatial Control of Gene Expression within a Scaffold by Localized Inducer Release

Baraniak, Priya R.; Nelson, Devin M.; Leeson, Cory E.; Katakam, Anand K.; Friz, Jennifer L.; Cress, Dean E.; Hong, Yi; Guan, Jianjun; Wagner, William R.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
26.97%
Gene expression can be controlled in genetically modified cells by employing an inducer/promoter system where presence of the inducer molecule regulates the timing and level of gene expression. By applying the principles of controlled release, it should be possible to control gene expression on a biomaterial surface by the presence or absence of inducer release from the underlying material matrix, thus avoiding alternative techniques that rely upon uptake of relatively labile DNA from material surfaces. To evaluate this concept, a modified ecdysone-responsive gene expression system was transfected into B16 murine cells and the ability of an inducer ligand, which was released from elastomeric poly(ester urethane) urea (PEUU), to initiate gene expression was studied. The synthetic inducer ligand was first loaded into PEUU to demonstrate extended release of the bioactive molecule at various loading densities over a one year period in vitro. Patterning films of PEUU variably-loaded with inducer resulted in spatially controlled cell expression of the gene product (green fluorescent protein, GFP). In porous scaffolds made from PEUU by salt leaching, where the central region was exclusively loaded with inducer, cells expressed GFP predominately in the loaded central regions whereas expression was minimal in outer regions where ligand was omitted. This scaffold system may ultimately provide a means to precisely control progenitor cell commitment in a spatially-defined manner in vivo for soft tissue repair and regeneration.

How ‘arm-twisting’ by the inducer triggers activation of the MalT transcription factor, a typical signal transduction ATPase with numerous domains (STAND)

Danot, Olivier
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
26.94%
Signal transduction ATPases with numerous domains (STAND) get activated through inducer-dependent assembly into multimeric platforms. This switch relies on the conversion of their nucleotide-binding oligomerization domain (NOD) from a closed, ADP-bound form to an open, ATP-bound form. The NOD closed form is stabilized by contacts with the arm, a domain that connects the NOD to the inducer-binding domain called the sensor. How the inducer triggers NOD opening remains unclear. Here, I pinpointed the NOD-arm interface of the MalT STAND transcription factor, and I generated a MalT variant in which this interface can be covalently locked on demand, thereby trapping the NOD in the closed state. By characterizing this locked variant, I found that the inducer is recognized in two steps: it first binds to the sole sensor with low affinity, which then triggers the recruitment of the arm to form a high-affinity arm-sensor inducer-binding site. Strikingly, this high-affinity binding step was incompatible with arm-NOD contacts maintaining the NOD closed. Through this toggling between two mutually exclusive states reminiscent of a single-pole double-throw switch, the arm couples inducer binding to NOD opening, shown here to precede nucleotide exchange. This scenario likely holds for other STANDs like mammalian NLR innate immunity receptors.

Impact of Residual Inducer on Titratable Expression Systems

Afroz, Taliman; Luo, Michelle L.; Beisel, Chase L.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 08/09/2015 EN
Relevância na Pesquisa
26.89%
Inducible expression systems are widely employed for the titratable control of gene expression, yet molecules inadvertently present in the growth medium or synthesized by the host cells can alter the response profile of some of these systems. Here, we explored the quantitative impact of these residual inducers on the apparent response properties of inducible systems. Using a simple mathematical model, we found that the presence of residual inducer shrinks the apparent dynamic range and causes the apparent Hill coefficient to converge to one. We also found that activating systems were more sensitive than repressing systems to the presence of residual inducer and the response parameters were most heavily dependent on the original Hill coefficient. Experimental interrogation of common titratable systems based on an L-arabinose inducible promoter or a thiamine pyrophosphate-repressing riboswitch in Escherichia coli confirmed the predicted trends. We finally found that residual inducer had a distinct effect on “all-or-none” systems, which exhibited increased sensitivity to the added inducer until becoming fully induced. Our findings indicate that residual inducer or repressor alters the quantitative response properties of titratable systems...

In vitro mutational analysis of the inducer binding site of lactose repressor

Chang, Wen-I
Fonte: Universidade Rice Publicador: Universidade Rice
ENG
Relevância na Pesquisa
27.09%
The inducer binding site of the E. coli lactose repressor has been examined by in vitro characterization of mutant proteins with amino acid substitutions at the hypothetical inducer binding site (Sams, C. F., Vyas, N. K., Quiocho, F. A. and Matthews, K. S. (1984) Nature 310, 429-430). Since the major force for sugar interaction comes from hydrogen bonding between the inducer and the hydrophilic side chains in the inducer binding site of lac repressor, Lys$sp{84}$, Asp$sp{88}$, Asp$sp{130}$ and Asp$sp{274}$ at the hypothetical inducer binding site were chosen to be substituted. Using site-directed mutagenesis, each site was substituted with four different amino acids that altered side chain length, polarity or charge. In addition, double mutations were introduced at Lys$sp{84}$ and Tyr$sp{282}$ sites in order to elucidate the role of Lys$sp{84}$ in subunit interaction. Through characterizing mutant proteins at the Lys$sp{84}$ site in vitro, including inducer binding properties, operator binding activities, immunoblotting pattern, and gel filtration behavior, we conclude that Lys$sp{84}$ is at the same subunit interface as Tyr$sp{282}$ and is not involved directly in the inducer binding site. A similar situation applies to Asp$sp{88}$...

EXAMINATION OF THE INTERACTION OF INDUCER WITH THE LACTOSE REPRESSOR PROTEIN

CHAKERIAN, ARTEMIS ELENA
Fonte: Universidade Rice Publicador: Universidade Rice
Tipo: Thesis; Text Formato: application/pdf
ENG
Relevância na Pesquisa
26.94%
The lactose repressor protein from the mutant E. coli BG185 contains valine at position 81 instead of alanine (Adler et al., 1972; Muller-Hill et al., 1975). The BG185 protein exhibits properties similar to the wild-type repressor-inducer complex. Kinetic measurements suggest that the structural transitions required for inducer binding are markedly impaired by the mutation. The fluorescence spectral shift in response to inducer binding was identical for mutant and wild-type proteins. This identity indicates direct effects of inducer binding on the tryptophan(s) near the sugar binding site rather than environmental changes consequent to conformational shifts. Analogy to the bacterial sugar binding proteins suggests that the alanine to valine change at position 81 in BG185 repressor yields a molecule that is fixed in a closed, sugar-binding conformation. Serine 193 in the lactose repressor protein was changed to alanine and threonine to assess the putative role of this residue in allowing/blocking binding of $\beta$-substituted D-galactosides. The results demonstrate that the side chain of amino acid 193 does not play a direct role in inducer binding. Cysteine 281 was changed to serine and alanine in order to ascertain the contribution of this residue to the pH effects on inducer binding. A decrease in IPTG binding affinity for both mutants indicates a role for this residue in the optimal function of repressor...

Analysis of Cavitation Instabilities in a Four-Blade Inducer

COUTIER-DELGOSHA, Olivier; DAZIN, Antoine; CAIGNAERT, Guy; BOIS, Gérard
Fonte: HPC - Hindawi Publishing Corporation Publicador: HPC - Hindawi Publishing Corporation
EN
Relevância na Pesquisa
36.74%
The cavitating behavior of a four-blade inducer tested in the LML laboratory large test facility is considered in the present paper. Experimental investigations based on unsteady pressure measurements and records from a six-component balance mounted on the inducer shaft are performed. Spectral analysis of the signals enables to detect several characteristic frequencies related to unbalanced two-phase flow patterns. The objective of the present paper is the understanding of the physical phenomena associated to these frequencies. Therefore, wavelet decomposition, flow visualizations, and direct analysis of the high-frequency force, moment, and pressure signals are applied. Results at nominal flow rate only are considered. Not only classical unbalanced cavitation patterns, but also unexpected flow organizations are discussed.; industrie

Influence of the Blade Number on Inducer Cavitating Behavior

COUTIER-DELGOSHA, Olivier; CAIGNAERT, Guy; BOIS, Gérard; LEROUX, Jean-Baptiste
Fonte: asme Publicador: asme
EN_US
Relevância na Pesquisa
36.62%
Effects of the blade number on the performance of a rocket engine turbopump inducer are investigated in the present paper. For that purpose, two inducers characterized by three blades and five blades, respectively, were manufactured and tested experimentally. The two inducers were designed on the basis of identical design flow rate and identical pressure elevation at nominal flow rate. The first part of the study focuses on the steady behavior of the inducers in cavitating conditions: evolutions of performance, torque, mass flow rate, and amplitude of radial forces on the shaft according to the inlet pressure are considered. Several flow rates and rotation speeds are investigated. Significant differences between the inducers are obtained concerning the critical cavitation number, the amplitude of the radial forces, and the organization of cavitation in the machinery. Cavitation instabilities are investigated in the second part of the study. Various flow patterns are detected accord- ing to the mass flow rate and the cavitation number.; industrie

Hexamethylenebisacetamide-resistant murine erythroleukemia cells have altered patterns of inducer-mediated chromatin changes.

Sheffery, M; Rifkind, R A; Marks, P A
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /06/1983 EN
Relevância na Pesquisa
26.94%
We determined inducer-mediated changes in chromatin structure near the globin genes in a variant line of murine erythroleukemia cells (MELC). The variant cell line, R1, was derived from the inducer-sensitive DS19 cell line by selection for inducer-resistance. R1 cells are resistant to induction of erythroid differentiation by hexamethylenebisacetamide (HMBA) whereas the parental line is HMBA-sensitive. Uninduced MELC (both inducer-sensitive DS19 cells and inducer-resistant R1 cells) have DNase I-sensitive sites in chromatin containing the alpha 1- and beta maj-globin genes. These nuclease-sensitive regions are located within the beta maj-globin second intervening sequence (IVS2) and near the alpha 1-globin gene 5' cap site. Culture with HMBA causes changes in chromatin structure in both parental and variant cell lines. In DS19 cells, the DNase I-sensitive site within the beta maj-globin IVS2 becomes more resistant to nuclease cleavage, and a new DNase I-sensitive region develops near the beta maj-globin cap site. In addition, the nuclease-sensitive region adjacent to the cap site of the alpha 1-globin gene increases, and a novel 5' nuclease-sensitive site is also established. In R1 cells, HMBA-mediated changes in chromatin structure are incomplete. The DNase I-sensitive site within the beta maj-globin IVS2 becomes more resistant to nuclease cleavage...

Immunoregulatory CD4+ CD45R+ suppressor/inducer T lymphocyte subsets and impaired cell-mediated immunity in patients with Down's syndrome.

Raziuddin, S; Elawad, M E
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /01/1990 EN
Relevância na Pesquisa
26.89%
The monoclonal antibodies 2H4 and 4B4 allow CD4+ and CD8+ T lymphocytes to be subdivided into CD45R+ and CDW29+ functional subpopulations. The CD4+ CD45R+ lymphocytes are designated as suppressor/inducer and CD4+ CDW29+ as helper/inducer subsets. Peripheral blood lymphocytes from 19 patients with Down's syndrome and 19 age- and sex-matched normal controls were analysed for the CD45R+ and CDW29+ subsets from the CD4+ and CD8+ T lymphocytes. The percentage of CD4+ CD45R+ cells (suppressor inducer) was markedly increased and of CD4+ CDW29+ cells (helper/inducer) decreased in all patients with Down's syndrome. In contract, the percentage of CD8+ CD45R+ and CD8+ CDW29+ subsets showed no major differences between patients with Down's syndrome and normal controls. Moreover, an alteration in the CD4+ and CD45R+ and CD4+ CDW29+ T cell subsets was accompanied by a markedly reduced proliferative response to phytohaemagglutinin and concanavalin A stimulation of the CD4+ T lymphocytes. Thus, a deficiency exists in patients with Down's syndrome in the CD4+ CDW29+ helper/inducer T cell subset which may contribute to their impaired cell-mediated immunity.

Effect of menadione sodium bisulfite, an inducer of plant defenses, on the dynamic of banana phytoalexin accumulation during pathogenesis

Borges, Andrés Antonio; Borges-Pérez, Andrés; Fernández Falcón, Marino
Fonte: American Chemical Society Publicador: American Chemical Society
Tipo: Artículo Formato: 2373 bytes; 4694906 bytes; text/plain; application/pdf
ENG
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3 pages, 2 figures.-- PMID: 12926878 [PubMed].-- Printed version published Aug 27, 2003.; Using an authentic sample of 2-hydroxy-9-(p-hydroxyphenyl)-phenalen-1-one, a banana phenalenone-type phytoalexin, we studied its dynamic of accumulation during pathogenesis of banana plants (Musa acuminata (AAA), Grand Nain) inoculated with Fusarium oxysporum f.sp. cubense (FOC), Race 4, the causal agent of Panama disease. The results obtained demonstrate that banana plants treated prior inoculation with menadione sodium bisulfite (MSB), an inducer of plant defenses, are capable of changing the dynamic of accumulation (higher amount and speed of biosynthesis) of this banana phytoalexin, biosynthesized by the banana plant during pathogenesis.