• Journal of Genetic Medicine
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• v.10 no.1
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• pp.47-51
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• 2013

Loeys-Dietz syndrome (LDS) is an autosomal dominant disorder caused by heterozygous mutations in the genes encoding transforming growth factor-${\beta}$ receptor type 1 or 2. It is typically characterized by a triad of hypertelorism, cleft palate or bifid uvula, and arterial tortuosity with aneurysm or dissection. Characteristic vascular abnormalities such as tortuosity, aneurysms, dissections, and stenosis are the most severe complications of LDS and can occur in the neurovascular system. We report a 5-year-old boy who presented with headaches and neurovascular abnormalities and was diagnosed with LDS with a novel mutation of the TGFBR1 gene. It is the first Korean report of neurovascular abnormalities in LDS.

• Biomolecules & Therapeutics
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• v.28 no.1
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• pp.98-103
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• 2020

Marfan syndrome (MFS), a connective tissue disorder caused by mutations in the fibrillin-1 (Fbn1) gene, has vascular manifestations including aortic aneurysm, dissection, and rupture. Its vascular pathogenesis is assumed to be attributed to increased transforming growth factor β (TGFβ) signaling and blockade of excessive TGFβ signaling has been thought to prevent dissection and aneurysm formation. Here, we investigated whether galunisertib, a potent small-molecule inhibitor of TGFβ receptor I (TβRI), attenuates aneurysmal disease in a murine model of MFS (Fbn1^C1039G/+) and compared the impact of galuninsertib on the MFS-related vascular pathogenesis with that of losartan, a prophylactic agent routinely used for patients with MFS. Fbn1^C1039G/+ mice were administered galunisertib or losartan for 8 weeks, and their ascending aortas were assessed for histopathological changes and phosphorylation of Smad2 and extracellular signal-regulated kinase 1/2 (Erk1/2). Mice treated with galunisertib or losartan barely exhibited phosphorylated Smad2, suggesting that both drugs effectively blocked overactivated canonical TGFβ signaling in Fbn1^C1039G/+ mice. However, galunisertib treatment did not attenuate disrupted medial wall architecture and only partially decreased Erk1/2 phosphorylation, whereas losartan significantly inhibited MFS-associated aortopathy and markedly decreased Erk1/2 phosphorylation in Fbn1^C1039G/+ mice. These data unexpectedly revealed that galunisertib, a TβRI inhibitor, showed no benefits in aneurysmal disease in MFS mice although it completely blocked Smad2 phosphorylation. The significant losartan-induced inhibition of both aortic vascular pathogenesis and Smad2 phosphorylation implied that canonical TGFβ signaling might not prominently drive aneurysmal diseases in MFS mice.

• Korean Journal of Environmental Agriculture
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• v.29 no.1
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• pp.77-85
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• 2010

Reactive oxygen species (ROS) are very harmful to living organisms due to the potential oxidation of membrane lipids, DNA, proteins, and carbohydrates. transformed E.coli strain QC 871, superoxide dismutase (SOD) double-mutant, with three sequence variant MnSOD1, MnSOD2, and MnSOD3 manganese superoxide dismutase (MnSOD) gene isolated from wheat. Although all QC 871 transformants grown at $37^{\circ}C$ expressed mRNA of MnSOD variants, only MnSOD2 transformant had functional SOD activity. MnSOD3 expressed active protein when grown at $22^{\circ}C$, however, MnSOD1 did not express functional protein at any growing and induction conditions. The sequence comparison of the wheat MnSOD variants revealed that the only amino acid difference between the sequence MnSOD2 and sequences MnSOD1 and 3 is phenylalanine/serine at position 58 amino acid. We made MnSOD2S58F gene, which was made by altering the phenylalaine to serine at position 58 in MnSOD2. The expressed MnSOD2S58F protein had functional SOD activity, even at higher levels than the original MnSOD2 at all observed temperatures. These data suggest that amino acid variation can result in highly active forms of MnSOD and the MnSOD2S58F gene can be an ideal target used for transforming crops to increase tolerance to environmental stresses.

• The Korean Journal of Mycology
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• v.21 no.4
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• pp.279-284
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• 1993

The metE gene coding for $N^{5}-methyl-H_{4}-folate;$ homocysteine methyltransferase from the basidiomycete Ganoderma lucidum was cloned by complementation of methionine-requiring mutants of E. coli. The size of a inserted DNA was about 1.54 kb and had 5 restriction enzyme sites. A physical map was constructed. Southern blot analysis confirmed the presence of a transforming DNA in the genome of Ganoderma lucidum. indicating the presence of a single copy.

• Archives of Pharmacal Research
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• v.22 no.1
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• pp.1-8
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• 1999

Transforming growth factor-$\beta$ (TGF-$\beta$) is the prototypical multifunctional cytokine, participating in the regulation of vital cellular activities such as proliferation and differentiations as well as a number of basic physiological functions. The effects of TGF-$\beta$ are critically dependent on the expression and distribution of a family of TGF-$\beta$ receptors, the TGF-$\beta$ types I, II, and III. It is now known that a wide variety of human pathology can be caused by aberrant expression and function of these receptors. the coding sequence of the type II receptor (RII) appears to render it uniquely susceptible to DNA replication errors in the course of normal cell division. By virtue of its key role in the regulation of cell proliferation, TGF-$\beta$ RII should be considered as a tumor suppressor gene. High levels of mutation in the TGF-$\beta$ RII gene have been observed in a wide range of primarily epithelial malignancies, including colon and gastric cancer. It appears likely that mutation of the TGF-$\beta$ RII gene may be a very critical step in the pathway of carcinogenesis.

• Journal of Microbiology and Biotechnology
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• v.21 no.11
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• pp.1101-1108
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• 2011

The rise in global energy demand has prompted researches on developing strategies for transforming coal into a cleaner fuel. This requires isolation of microbes with the capability to degrade complex coal into simpler substrates to support methanogenesis in the coal beds. In this study, aerobic bacteria were isolated from an Indian coal bed that can solubilize and utilize coal as the sole source of carbon. The six bacterial isolates capable of growing on coal agar medium were identified on the basis of their 16S rRNA gene sequences, which clustered into two groups; Group I isolates belonged to the genus Rhizobium, whereas Group II isolates were identified as Chelatococcus species. Out of the 4 methods of whole genome fingerprinting (ERIC-PCR, REP-PCR, BOX-PCR, and RAPD), REP-PCR showed maximum differentiation among strains within each group. Only Chelatococcus strains showed the ability to solubilize and utilize coal as the sole source of carbon. On the basis of 16S rRNA gene sequence and the ability to utilize different carbon sources, the Chelatococcus strains showed maximum similarity to C. daeguensis. This is the first report showing occurrence of Rhizobium and Chelatococcus strains in an Indian coal bed, and the ability of Chelatococcus isolates to solubilize and utilize coal as a sole source of carbon for their growth.

• Molecules and Cells
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• v.45 no.7
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• pp.435-443
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• 2022

In response to environmental changes, signaling pathways rewire gene expression programs through transcription factors. Epigenetic modification of the transcribed RNA can be another layer of gene expression regulation. N⁶-adenosine methylation (m⁶A) is one of the most common modifications on mRNA. It is a reversible chemical mark catalyzed by the enzymes that deposit and remove methyl groups. m⁶A recruits effector proteins that determine the fate of mRNAs through changes in splicing, cellular localization, stability, and translation efficiency. Emerging evidence shows that key signal transduction pathways including TGFβ (transforming growth factor-β), ERK (extracellular signal-regulated kinase), and mTORC1 (mechanistic target of rapamycin complex 1) regulate downstream gene expression through m⁶A processing. Conversely, m⁶A can modulate the activity of signal transduction networks via m⁶A modification of signaling pathway genes or by acting as a ligand for receptors. In this review, we discuss the current understanding of the crosstalk between m⁶A and signaling pathways and its implication for biological systems.

• Journal of Plant Biotechnology
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• v.34 no.4
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• pp.307-312
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• 2007

Chlamydomonas reinhardtii was transformed with the coding sequence of the Tombus virus gene p19 to determine whether the gene functions as an RNAi suppressor in C. reinhardtii. Transformants were confirmed to have 1 to several copies of p19 gene in their chromosomes. When an RNAi strain of C. reinhardtii generated by transforming the inverted repeat (IR) sequence homologous to the 3'UTR region of the MAA7 gene was re-transformed with the gene p19, MAA7 transcript levels of transformants fluctuated and proliferation of trans-formants on the medium containing 5-FI was suppressed. Overall results suggest that p19-mediated silencing suppression works at a low level in C. reinhardtii because of difference in codon usage resulting in weak P19 expression unless p19-mediated silencing suppression in C. reinhardtii works in a different manner from higher plants.

• Korean Journal of Microbiology
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• v.42 no.4
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• pp.246-251
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• 2006

A lot of mutants which cannot initiate sexual development were screened and several loci including nsdA, nsdB, nsdC, and nsdD were identified in homothallic ascomycetes Aspergillus nidulans. The NSD206, which has nsdC6 allele, showed typical phenotype of NSD (Never in sexual development) mutants. The nsdC gene was cloned by transforming NSDP697 ($nsdC^-$, $pryG^-$) with AMA1-NotI genomic library. The transforming library DNA recovered from several transformants showing wild phenotype carried about 10 kb genomic DNA insert. The DNA sequence of nsdC was analysed using GPS (Genome priming system). The nsdC gene has an open reading frame (ORF) of 1,929 bp encoding a putative polypeptide of 643 amino acids. The NsdC carries $C_2H_2C_2H_2C_2HC$ type zinc finger DNA binding domains in the middle of the polypeptide. A coiled-coil domain at its C terminus were also found. In nsdC6 allele, a single T insertion was occurred between 407-408 bp leading to the frameshift mutation and early termination of translation producing the truncated protein which has only 139 amino acids.

• Journal of Microbiology and Biotechnology
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• v.12 no.1
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• pp.121-129
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• 2002

Using recombinant Chinese hamster ovary (CHO) cells, strategies for developing high producers for the recombinant human Transforming Growth $Factor-{\beta}1$ ($TGF-{\beta}1$) protein are proposed and their physiological characteristics in cell cultures were investigated. $TGF-{\beta}1$ is a pleiotrophic polypeptide involved in various biological activities, including cell growth, differentiation, and deposition of extracellular matrix proteins. The CHO cells included human $TGF-{\beta}1$ cDNA in conjunction with a dihydrofolate reductase (DHFR) gene, which was cotransfected into the cells to amplify the transfected $TGF-{\beta}1$ cDNA. As a first-round screening of the transfected cells, a relatively high $TGF-{\beta}1$-producing cell line was selected, and then, it acquired a resistance to increasing concentrations of methotrexate (MTX) up to $60{\mu}M$,resulting in a significant improvement in its $TGF-{\beta}1$ biosynthetic ability. After applying a monoclonal selection strategy to the MTX-resistant cells, more productive cells were screened, including the APP-3, App-5, and App-8 cell lines. These high producers were compared with two other cell lines (AP-l cell line without amplification of transfected $TGF-{\beta}1$ cDNA and nontransfectant of $TGF-{\beta}1$ cDNA) in terms of cell growth, $TGF-{\beta}1$ productivity, sugar uptake, and byproduct formation, in the presence or absence of MTX in the culture medium. Consequently, both monoclonal selection as well as an investigation of the physiological characteristics were found to be needed for the efficient screening of higher $TGF-{\beta}1$ producers, even after the transfection and amplification of the transfected gene.