• Molecules and Cells
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• v.37 no.3
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• pp.220-225
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• 2014

Suppression of bone morphogenetic protein (BMP) signaling induces neural induction in the ectoderm of developing embryos. BMP signaling inhibits neural induction via the expression of various neural suppressors. Previous research has demonstrated that the ectopic expression of dominant negative BMP receptors (DNBR) reduces the expression of target genes down-stream of BMP and leads to neural induction. Additionally, gain-of-function experiments have shown that BMP downstream target genes such as MSX1, GATA1b and Vent are involved in the suppression of neural induction. For example, the Vent1/2 genes are involved in the suppression of Geminin and Sox3 expression in the neural ectodermal region of embryos. In this paper, we investigated whether PV.1, a BMP downstream target gene, negatively regulates the expression of FoxD5b, which plays a role in maintaining a neural progenitor population. A promoter assay and a cyclohexamide experiment demonstrated that PV.1 negatively regulates FoxD5b expression.

• IMMUNE NETWORK
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• v.8 no.1
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• pp.21-28
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• 2008

Background: A co-inhibitory molecule, B7-H4, is believed to negatively regulate T cell immunity by suppressing T cell proliferation and inhibiting cytokine production. However, the mechanism behind B7-H4-mediated tolerance remains unclear. Methods: Balb/c $(H-2^d)$ mice were fed with dendritic cell line, DC2.4 $(H-2^d)$ every day for 10 days. Meantime, mice were hydrodynamically injected with recombinant plasmid expressing B7-H4 fusion protein (B7-H4.hFc) or hFc via tail vein. One day after last feeding, mice were immunized with allogeneic B6 spleen cells. 14 days following immunization, mice were challenged with B6 spleen cells to ear back and the ear swelling was determined the next day. Subsequently, a mixed lymphocyte reaction (MLR) was also performed and cytokines profiles from the reaction were examined by sandwich ELISA. Frequency of immunosuppressive cell population was assayed with flow cytometry and mRNA for FoxP3 was determined by RT-PCR. Results: Tolerant mice given plasmid expressing B7-H4.hFc showed a significant reduction in ear swelling compared to control mice. In addition, T cells from mice given B7-H4.hFc plasmid revealed a significant hyporesponsiveness of T cells against allogeneic spleen cells and showed a significant decrease in Th1 and Th2 cytokines such as IFN-${\gamma}$, IL-5, and TNF-${\alpha}$. Interestingly, flow cytometric analysis showed that the frequency of CD4+CD25+FoxP3+ Tregs in spleen was increased in tolerant mice given recombinant B7-H4.hFc plasmid compared to control group. Conclusion: Our results demonstrate that B7-H4 synergistically potentiates oral tolerance induced by allogeneic cells by increasing the frequency of FoxP3+ CD4+CD25+ Treg and reducing Th1 and Th2 cytokine production.

• IMMUNE NETWORK
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• v.20 no.6
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• pp.50.1-50.11
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• 2020

Osteoporosis is prevalent in elderly women and it may cause dental implant failure. In particular, estrogen deficiency in postmenopausal women leads to higher rates of osteoporosis prevalence. Immune cell-mediated effects involving the development of osteoporosis have been studied previously; however, the role of IL-10-producing regulatory B (B10) cells in osteoporosis is largely unclear. Here, we examined the role of B10 cells in osteoporosis. C57BL/6 mice were subjected to ovariectomy (OVX). Fifteen weeks after OVX surgery, the first molar of the right maxillary was extracted, and twenty-four weeks after OVX surgery, serous progression of osteoporosis was observed in the alveolar bone. Moreover, the proportion of CD19⁺CD5⁺CD1d^high regulatory B cells, B10, and CD4⁺CD25⁺FoxP3⁺ regulatory T cells from the spleen of OVX mice decreased during the progression of osteoporosis, compared to controls. In contrast to regulatory cells, IL-17-producing Th (Th17) cell levels were increased in OVX mice. Adoptive transfer of B10 cells to OVX mice led to a decrease in Th17 cell abundance and inhibited the development of osteoporosis in the alveolar bone from OVX mice. Thus, our results suggest that B10 cells may help suppress osteoporosis development.

• Molecules and Cells
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• v.41 no.12
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• pp.1061-1071
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• 2018

From Xenopus embryo studies, the BMP4/Smad1-targeted gene circuit is a key signaling pathway for specifying the cell fate between the ectoderm and neuro-ectoderm as well as the ventral and dorsal mesoderm. In this context, several BMP4/Smad1 target transcriptional factors have been identified as repressors of the neuro-ectoderm. However, none of these direct target transcription factors in this pathway, including GATA1b, Msx1 and Ventx1.1 have yet been proven as direct repressors of early neuro-ectodermal gene expression. In order to demonstrate that Ventx1.1 is a direct repressor of neuro-ectoderm genes, a genome-wide Xenopus ChIP-Seq of Ventx1.1 was performed. In this study, we demonstrated that Ventx1.1 bound to the Ventx1.1 response cis-acting element 1 and 2 (VRE1 and VRE2) on the promoter for zic3, which is a key early neuro-ectoderm gene, and this Ventx1.1 binding led to repression of zic3 transcription. Site-directed mutagenesis of VRE1 and VRE2 within zic3 promoter completely abolished the repression caused by Ventx1.1. In addition, we found both the positive and negative regulation of zic3 promoter activity by FoxD5b and Xcad2, respectively, and that these occur through the VREs and via modulation of Ventx1.1 levels. Taken together, the results demonstrate that the BMP4/Smad1 target gene, Ventx1.1, is a direct repressor of neuro-ectodermal gene zic3 during early Xenopus embryogenesis.

• Journal of Animal Science and Technology
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• v.55 no.5
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• pp.359-365
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• 2013

Estimate breeding value can be used as single trait animal model was developed directly using the Fortran language program. The program is based on data computed by using the indirect method repeatedly. The program develops a common algorithm and imprves efficiency. Algorithm efficiency was compared between the two programs. Estimated using the solution is easy to farm and brand the service, pedigree data base was associated with the development of an improved system. The existing program that uses the single trait animal model and the comparative analysis of efficiency is weak because the estimation of the solution and the conventional algorithm programmed through regular formulation involve many repetition; therefore, the newly developed algorithm was conducted to improve speed by reducing the repetition. Single trait animal model was used to analyze Gauss-Seidel iteration method, and the aforesaid two algorithms were compared thorough the mixed model equation which is used the most commonly in estimating the current breeding value by applying the procedures such as the preparation of information necessary for modelling, removal of duplicative data, verifying the parent information of based population in the pedigree data, and assigning sequential numbers, etc. The existing conventional algorithm is the method for reading and recording the data by utilizing the successive repetitive sentences, while new algorithm is the method for directly generating the left hand side for estimation based on effect. Two programs were developed to ensure the accurate evaluation. BLUPF90 and MTDFREML were compared using the estimated solution. In relation to the pearson and spearman correlation, the estimated breeding value correlation coefficients were highest among all traits over 99.5%. Depending on the breeding value of the high correlation in Model I and Model II, accurate evaluation can be found. The number of iteration to convergence was 2,568 in Model I and 1,038 in Model II. The speed of solving was 256.008 seconds in Model I and 235.729 seconds in Model II. Model II had a speed of approximately 10% more than Model I. Therefore, it is considered to be much more effective to analyze large data through the improved algorithm than the existing method. If the corresponding program is systemized and utilized for the consulting of farm and industrial services, it would make contribution to the early selection of individual, shorten the generation, and cultivation of superior groups, and help develop the Hanwoo industry further through the improvement of breeding value based enhancement, ultimately paving the way for the country to evolve into an advanced livestock country.