The mechanisms of regulation of I-Aβ gene expression in the murine major histocompatibilitycomplex by transcriptional repression are reviewed. Active and passive repression mechanisms are presented. ...The transcription factor PU.1 actively inhibits the expression of I-Aβ through the binding to a DNA sequence near the Y box, a
cis-element in the promoter necessary for transcription. This interaction probably interferes with the preinitiation complex assembly.
NF-Y is a transcription factor that binds to the Y box and has two constituents: NF-YA (thatbinds weakly to DNA) and NF-YB (that increases the binding of NF-YA to DNA). The dbpA protein represses the expression of I-Aβ by a quenching mechanism, forming a complex with NF-YA and the dbpB protein by sequestering the NF-YB protein. A similar mechanism is observed with the glucocorticoid receptor that binds to the X-box binding proteins and inhibits their interaction with the X box.
These results are examples of cross-talk between proteins, which may help us to understandthe regulation of I-Aβ gene expression.
Adenosine is a potent endogenous anti-inflammatory agent released by cells in metabolically unfavorable conditions, such as hypoxia or ischemia. Adenosine modulates different functional activities in ...macrophages. Some of these activities are believed to be induced through the uptake of adenosine into the macrophages, while others are due to the interaction with specific cell surface receptors. In murine bone marrow-derived macrophages, the use of different radioligands for adenosine receptors suggests the presence of A2B and A3 adenosine receptor subtypes. The presence of A2B receptors was confirmed by flow cytometry using specific Abs. The A2B receptor is functional in murine macrophages, as indicated by the fact that agonists of A2B receptors, but not agonists for A1, A2A, or A3, lead to an increase in cAMP levels. IFN-gamma up-regulates the surface protein and gene expression of the A2B adenosine receptor by induction of de novo synthesis. The up-regulation of A2B receptors correlates with an increase in cAMP production in macrophages treated with adenosine receptor agonist. The stimulation of A2B receptors by adenosine or its analogues inhibits the IFN-gamma-induced expression of MHC class II genes and also the IFN-gamma-induced expression of nitric oxide synthase and of proinflammatory cytokines. Therefore, the up-regulation of the A2B adenosine receptor expression induced by IFN-gamma could be a feedback mechanism for macrophage deactivation.
Adenosine is a potent endogenous anti-inflammatory agent released by cells in metabolically unfavorable conditions, such as hypoxia or ischemia. Adenosine modulates different functional activities in ...macrophages. Some of these activities are believed to be induced through the uptake of adenosine into the macrophages, while others are due to the interaction with specific cell surface receptors. In murine bone marrow-derived macrophages, the use of different radioligands for adenosine receptors suggests the presence of A sub(2B) and A sub(3) adenosine receptor subtypes. The presence of A sub(2B) receptors was confirmed by flow cytometry using specific Abs. The A sub(2B) receptor is functional in murine macrophages, as indicated by the fact that agonists of A sub(2B) receptors, but not agonists for A sub(1), A sub(2A), or A sub(3), lead to an increase in cAMP levels. IFN- gamma up-regulates the surface protein and gene expression of the A sub(2B) adenosine receptor by induction of de novo synthesis. The up-regulation of A sub(2B) receptors correlates with an increase in cAMP production in macrophages treated with adenosine receptor agonist. The stimulation of A sub(2B) receptors by adenosine or its analogues inhibits the IFN- gamma -induced expression of MHC class II genes and also the IFN- gamma -induced expression of nitric oxide synthase and of proinflammatory cytokines. Therefore, the up-regulation of the A sub(2B) adenosine receptor expression induced by IFN- gamma could be a feedback mechanism for macrophage deactivation.
Two novel point mutations in the 3-hydroxy-3-methylglutaryl coenzyme A lyase gene were found in a French patient with double heterozygous 3-hydroxy-3-methylglutaric aciduria. Amplification by reverse ...transcriptase–polymerase chain reaction of the mRNA using five different pairs of oligonucleotides produced no differences in the fragments amplified with respect to the control. Single-strand conformation polymorphism analysis showed that only one amplified fragment was different in the patient vs. control. Sequencing of the amplified fragments showed two missense point mutations, A698G and T788C, each of them mixed with the wild-type sequence. These mutations produced the changes H233R and L263P, leading to changes in the enzyme activity, which was largely abolished. The father and one brother of the proband were heterozygous for the L263P mutation and the mother and one daughter were heterozygous for the H233R mutation, which confirms the double-heterozygous character of the patient. Another sibling was free of the mutations. An enzymatic restriction analysis has been proposed to screen the occurrence of these two mutations in future patients.
Hepatocytes show a Na super(+)-dependent nucleoside transport activity that is kinetically heterogeneous and consistent with the expression of at least two independent concentrative Na ...super(+)-coupled nucleoside transport systems. So far, only a single nucleoside carrier-related cDNA (SPNT) has been isolated from liver cells. This cDNA presumably encodes a plasma membrane protein responsible for Na super(+)-dependent purine nucleoside transport activity. Thus, the liver must express, at least, a second nucleoside transporter which should be pyrimidine-preferring. Homology cloning using RT-PCR revealed that a second isoform is indeed present in liver. This second isoform turned out to be identical to the `epithelial-specific isoform' called cNT1, which shows in fact high specificity for pyrimidine nucleosides. Although cNT1 mRNA is present at lower amounts than SPNT mRNA, the amounts of cNT1 protein, when measured using isoform-specific polyclonal antibodies, were even higher than the SPNT protein levels. Moreover, partially purified basolateral plasma membrane vesicles from liver were enriched in the SPNT but not in the cNT1 protein, which suggests that the subcellular localization of these carrier proteins is different. SPNT and cNT1 protein amounts in crude membrane extracts from 6 h-regenerating rat livers are higher than in the preparations from sham-operated controls (3.5- and 2-fold, respectively). These results suggest that liver parenchymal cells express at least two different isoforms of concentrative nucleoside carriers, the cNT1 and SPNT proteins, which show differential regulation and subcellular localization.
Cycloheximide, an antibiotic inhibiting protein synthesis, exerted a toxic effect on different developmental stages egg, larva and adult of Drosophila melanogaster. At the egg stage the early embryos ...were most sensitive. With larvae, a strong decrease in viability was found, with no sex difference. In adults, there was a dose-effect relationship, mortality increasing with concentration. At 10 and 15 mM, males were more sensitive than females. There were consistent differences between the control and cycloheximide-fed females in respect of the average number of eggs deposited and offspring produced.
We have identified a new human cDNA (y+L amino acid transporter-1 (y+LAT-1)) that induces system y+L transport activity with 4F2hc (the surface antigen 4F2 heavy chain) in oocytes. Human y+LAT-1 is a ...new member of a family of polytopic transmembrane proteins that are homologous to the yeast high affinity methionine permease MUP1. Other members of this family, the Xenopus laevis IU12 and the human KIAA0245 cDNAs, also co-express amino acid transport activity with 4F2hc in oocytes, with characteristics that are compatible with those of systems L and y+L, respectively. y+LAT-1 protein forms a approximately 135-kDa, disulfide bond-dependent heterodimer with 4F2hc in oocytes, which upon reduction results in two protein bands of approximately 85 kDa (i.e. 4F2hc) and approximately 40 kDa (y+LAT-1). Mutation of the human 4F2hc residue cysteine 109 (Cys-109) to serine abolishes the formation of this heterodimer and drastically reduces the co-expressed transport activity. These data suggest that y+LAT-1 and other members of this family are different 4F2 light chain subunits, which associated with 4F2hc, constitute different amino acid transporters. Human y+LAT-1 mRNA is expressed in kidney >> peripheral blood leukocytes >> lung > placenta = spleen > small intestine. The human y+LAT-1 gene localizes at chromosome 14q11.2 (17cR approximately 374 kb from D14S1350), within the lysinuric protein intolerance (LPI) locus (Lauteala, T., Sistonen, P. , Savontaus, M. L., Mykkanen, J., Simell, J., Lukkarinen, M., Simmell, O., and Aula, P. (1997) Am. J. Hum. Genet. 60, 1479-1486). LPI is an inherited autosomal disease characterized by a defective dibasic amino acid transport in kidney, intestine, and other tissues. The pattern of expression of human y+LAT-1, its co-expressed transport activity with 4F2hc, and its chromosomal location within the LPI locus, suggest y+LAT-1 as a candidate gene for LPI.
In order to map and identify the glycoprotein-encoding gene from bovine herpesvirus type 1 (BHV-1), homologous to the gE glycoprotein from herpes simplex virus type 1 (HSV-1), a region of the unique ...short sequence from the BHV-1 genome has been sequenced. The sequenced region contains an ORF coding for a polypeptide of 575 amino acids (aa). The aa sequence presents substantial similarity to that of the glycoprotein gE from HSV-1 and to homologous proteins of related viruses such as pseudorabies virus, equine herpesvirus type 1 and varicella zoster virus. The aa sequence presents additional characteristics compatible with the structure of a viral glycoprotein: signal peptide, putative glycosylation sites and a long C-terminal transmembrane alpha-helix.
The study of the magnetic characteristics and constructive shapes of conductive materials, allows a better use of Its electrical characteristics, reducing the maintenance and extending the life of ...the electrical machines. The improvements obtained on the torque with low currents using rotor with spiral sheets are analysed on this paper. To have a complete study, several rotors and stators have been built to verify the electromagnetic variations on the three-phase asynchronous motors where they combine different constructive and mechanical characteristics of the related elements: changing inertias, constructive materials, and the geometrical shapes and disposition of the sheets. These different types of motors have been first tested in the laboratory, them, are simulated using computer aided tools (Matlab-Simulink). In particular four stators (1000 rpm, 1500 rpm, 1500 rpm-type A, and 3000 rpm) having the same constructive parameters, have been tested with the following rotors: solid rotor, solid rotor with diamagnetic rings, drag cup, and simple and double squirrel cage rotor. All these results have been compared to those obtained with the seven variants of spiral sheet rotor, presented on this paper. It has been demonstrated that It is possible to considerably reduce the starting currents and therefore reducing the maintenance and extending the life of motors, without any negative consequence on the starting torque.
PDF
