158 research outputs found
Activation of connective tissue growth factor gene by the c-Maf and Lc-Maf transcription factors
No full textThe Maf family of transcription factors is expressed during development of various organs and tissues, and is involved in a variety of developmental and cellular differentiation processes. We previously found that c-maf and mafB are strongly expressed in hypertrophic chondrocytes during cartilage development. Connective tissue growth factor (CTGF) is also expressed in hypertrophic chondrocytes. Adenovirus mediated introduction of c-maf gene into the mouse fibroblast cell line C3H10T1/2 strongly induced CTGF expression. CTGF can be induced by TGF-β via the SMAD pathway; however, the c-Maf could not induce TGF-β, nor could TGF-β induce the c-Maf, suggesting that activation of CTGF by Maf is TGF-β independent. Reporter transfection analysis using C3H10T1/2 cells shows that c-Maf stimulates a CTGF reporter gene. Lc-Maf, a splice variant of c-Maf containing an extra 10 amino acids in the carboxyl terminus, was a stronger inducer of the CTGF reporter gene than c-Maf. Chromatin immunoprecipitation analysis showed that c-Maf binds to the promoter region of the CTGF gene, indicating that Maf directly activates the CTGF gene. Gel mobility shift assays indicated that c-Maf binds to the region near the transcription initiation site of CTGF gene. Taken together, these data indicate that the CTGF gene is a target of c-Maf and Lc-Maf in cartilage development
Immunolocalization of cyclin D1 in the developing lens of c-maf -/- mice
No full textThe maf gene encodes a transcription factor protein containing a typical basic/leucine zipper domain structure, a motif for protein dimerization and DNA binding. It has been demonstrated that maf family genes have important roles in embryonic development and cellular differentiation. In this study, localization of cyclin D1, one of the cell cycle-related molecules, was examined immunohistochemically in developing lens cells of c-maf knockout (-/-) mice. At embryonic day 14 in wild-type mice, lens cells consisted of round epithelial cells in a single layer and regularly arranged elongated lens cells, indicating primary lens fiber cells. Cyclin D1-positive nuclei were observed in the lens epithelial cells, whereas cyclin D1 was not detected in the primary lens fiber cells. In c-maf -/- mice, a variety of round epithelial cells were located in the anterior and posterior lens. Many cyclin D1-positive nuclei were observed in lens epithelial cells as well as posterior lens cells. These results are consistent with c-maf playing a role in the regulation of cyclin D1 in developing lens cells
Inhibition of Small Maf Function in Pancreatic β-Cells Improves Glucose Tolerance Through the Enhancement of Insulin Gene Transcription and Insulin Secretion
No full textThe large-Maf transcription factor v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA) has been found to be crucial for insulin transcription and synthesis and for pancreatic beta-cell function and maturation. However, insights about the effects of small Maf factors on beta-cells are limited. Our goal was to elucidate the function of small-Maf factors on beta-cells using an animal model of endogenous small-Maf dysfunction. Transgenic (Tg) mice with beta-cell-specific expression of dominant-negative MafK (DN-MafK) experiments, which can suppress the function of all endogenous small-Mafs, were fed a high-fat diet, and their in vivo phenotypes were evaluated. Phenotypic analysis, glucose tolerance tests, morphologic examination of beta-cells, and islet experiments were performed. DN-MafK-expressed MIN6 cells were also used for in vitro analysis. The results showed that DN-MafK expression inhibited endogenous small-Maf binding to insulin promoter while increasing MafA binding. DN-MafK Tg mice under high-fat diet conditions showed improved glucose metabolism compared with control mice via incremental insulin secretion, without causing changes in insulin sensitivity or MafA expression. Moreover, up-regulation of insulin and glucokinase gene expression was observed both in vivo and in vitro under DN-MafK expression. We concluded that endogenous small-Maf factors negatively regulates beta-cell function by competing for MafA binding, and thus, the inhibition of small-Maf activity can improve beta-cell function
A heterozygous c-Maf transactivation domain mutation causes congenital cataract and enhances target gene activation
No full textMAF, one of a family of large Maf bZIP transcription factors, is mutated in human developmental ocular disorders that include congenital cataract, microcornea, coloboma and anterior segment dysgenesis. Expressed early in the developing lens vesicle, it is central to regulation of lens crystallin gene expression. We report a semi-dominant mouse c-Maf mutation recovered after ENU mutatgenesis which results in the substitution, D90V, at a highly conserved residue within the N-terminal 35 amino-acid minimal transactivation domain (MTD). Unlike null and loss-of-function c-Maf mutations, which cause severe runting and renal abnormalities, the phenotype caused by the D90V mutation is isolated cataract. In reporter assays, D90V results in increased promoter activation, a situation similar to MTD mutations of NRL that also cause human disease. In contrast to wild-type protein, the c-Maf D90V mutant protein is not inhibited by protein kinase A-dependent pathways. The MTD of large Maf proteins has been shown to interact with the transcriptional co-activator p300 and we demonstrate that c-Maf D90V enhances p300 recruitment in a cell-type dependent manner. We observed the same for the pathogenic human NRL MTD mutation S50T, which suggests a common mechanism of action. NRL MTD mutation S50T, which suggests a common mechanism of action. MTD mutation S50T, which suggests a common mechanism of action. © The Author 2007. Published by Oxford University Press. All rights reserved
MAF 6
No full textThe story here is on 6 to 21 of this booklet with circled page numbers. This is a strong version of an ancient fable. The rivers love to chat with each other, but they never want to mention the sea, because the sea turns them into salt water. They confront the sea, which is well pictured as a stern older man from the cover on. The sea's answer is: Very well, stop flowing into me. The rivers, whatever they do, cannot stop flowing into the sea. The foolish rivers realised that there was no escape from the sea and stopped complaining after that. The booklet is one of five booklets from this series ordered from The Book Depository in the UK. I suspect that some further members of the series will elude me.Retold by Aromal
MAF 5
No full textThe story here is on 6 to 21 of this booklet with circled page numbers. In this version, the frog gets tired on a friendly journey together. The frog then has the bright idea to tie a string between his back leg and one of the mouse's forelegs. (That part of the story has it backwards. A mouse back leg needs to be tied to a frog foreleg.) So we will always run together. The bright idea works: the mouse runs and the frog leaps. One of the story's best illustrations is on 14-15, and it gets repeated as the cover illustration. At a stream, the frog suggests to the frightened mouse that the latter can sit on the back of the former. The trip goes well and both are singing happily. Then the hawk appears, swoops down, and catches the mouse. Somewhat surprisingly, the mouse and frog are still tied to each other. The hawk promptly eats them both. An excellent last illustration shows the hawk in silhouette flying into the sunset with the mouse in a claw and the frog suspended below (21). This is a curious solution to the story's issues. I would judge it not totally satisfying. The booklet is one of five booklets from this series ordered from The Book Depository in the UK. I suspect that some further members of the series will elude me.Retold by Aromal
MAF 1
No full textHere is a good dramatization of the Aesopic fable expressing that reconciliation may not be possible in every case. Here the venomous snake kills a man's son, and the man reacts by using an axe to cut off the snake's tail. Both man and snake lie in wait for each other for some time to do more harm to the other. Then the man decides that it is time to reconcile with the snake, but the snake was wiser than the man (19). Don't be a fool. You cannot forget your son and I will not be able to forget my lost tail. We will always be enemies. Please go away. The last two-page image in strong silhouette shows the farmer trudging home dragging his axe with a heavy heart. Lively art. The cover shows the happy family of three before the unfortunate incident. I have ordered five more booklets from this series, but I suspect that some further members of the series will elude me.Retold by Aromal
Molecular basis of ligand-dependent regulation of NadR, the transcriptional repressor of meningococcal virulence factor NadA
No full textNeisseria adhesin A (NadA) is present on the meningococcal surface and contributes to adhesion to and invasion of human cells. NadA is also one of three recombinant antigens in the recently-approved Bexsero vaccine, which protects against serogroup B meningococcus. The amount of NadA on the bacterial surface is of direct relevance in the constant battle of host-pathogen interactions: it influences the ability of the pathogen to engage human cell surface-exposed receptors and, conversely, the bacterial susceptibility to the antibody-mediated immune response. It is therefore important to understand the mechanisms which regulate nadA expression levels, which are predominantly controlled by the transcriptional regulator NadR (Neisseria adhesin A Regulator) both in vitro and in vivo. NadR binds the nadA promoter and represses gene transcription. In the presence of 4-hydroxyphenylacetate (4-HPA), a catabolite present in human saliva both under physiological conditions and during bacterial infection, the binding of NadR to the nadA promoter is attenuated and nadA expression is induced. NadR also mediates ligand-dependent regulation of many other meningococcal genes, for example the highly-conserved multiple adhesin family (maf) genes, which encode proteins emerging with important roles in host-pathogen interactions, immune evasion and niche adaptation. To gain insights into the regulation of NadR mediated by 4-HPA, we combined structural, biochemical, and mutagenesis studies. In particular, two new crystal structures of ligand-free and ligand-bound NadR revealed (i) the molecular basis of ‘conformational selection’ by which a single molecule of 4-HPA binds and stabilizes dimeric NadR in a conformation unsuitable for DNA-binding, (ii) molecular explanations for the binding specificities of different hydroxyphenylacetate ligands, including 3Cl,4-HPA which is produced during inflammation, (iii) the presence of a leucine residue essential for dimerization and conserved in many MarR family proteins, and (iv) four residues (His7, Ser9, Asn11 and Phe25), which are involved in binding 4-HPA, and were confirmed in vitro to have key roles in the regulatory mechanism in bacteria. Overall, this study deepens our molecular understanding of the sophisticated regulatory mechanisms of the expression of nadA and other genes governed by NadR, dependent on interactions with niche-specific signal molecules that may play important roles during meningococcal pathogenesis
MAF 4
No full textThe story here is on 6 to 21 of this booklet with circled page numbers. The clever fox and the dumb ass become friends, but when they encounter a lion, the fox offers to deliver up the ass. He does so by getting the ass into a ditch. When the lion sees that the ass is caught, he devours the fox. Perhaps the best illustration is that reproduced on the cover: the surprising appearance of the lion terrifies the ass, but the fox immediately starts plotting (12-13). This is one of five booklets from this series ordered from The Book Depository in the UK. I suspect that some further members of the series will elude me.Retold by Aromal
On the semiclassical JWKB and MAF solutions of the uniformly lengthening pendulum via change of dependent variable in the Bessel's equation
No full textSemiclassical JWKB method and method of modified Airy functions (MAF) are the fundamental conventional tools in quantum mechanical and optical waveguide systems and yet their classical mechanical applicability has somehow escaped much attention. In this work, semiclassical JWKB and MAF solution of a classical mechanical problem regarding the Lengthening Pendulum (LP) is being studied to reinforce the power of the semiclassical methods in this aspect. Here, JWKB and MAF solutions of the associated Bessel's equation is being obtained by transforming it first into one of the normal forms via change of dependent variable on the contrary to our previous work where change of independent variable was used for the JWKB solution. By the same motivation for the suggested change of dependent variable here, we once again, obtain advantageous results in comparison to the conventional numerical exact solutions given in the literature where adiabatic LP systems with very low lengthening rates are required. We obtain both JWKB and MAF approximated Bessel functions successfully and our semiclassical solutions for the LP system works with a great accuracy even for much higher lengthening rates in comparison to these conventional numerical methods. Here we study under what conditions our semiclassical solutions can give accurate results by using the conventional JWKB and MAF applicability criteria. In effect, the semiclassical JWKB and MAF methods which is normally known to be used in quantum mechanical and optical waveguide systems are being used to solve the pure classical-mechanical LP system successfully and advantageously here and the applicability criteria of these semiclassical methods in terms of the physical LP system parameters are being determined and presented. © 2021 The Author(s
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