• 한국가축번식학회지
• /
• 제24권1호
• /
• pp.41-47
• /
• 2000

성선자극호르몬 수용체 (LH/CGR)는 7번 막을 통과하는 수용체의 일종이다. LH/CGR의 유전자 돌연변이 질환은 남성에 있어서 이들 수용체가 조기에 발현되어 조기 성숙의 원인이 된다. 이러한 수용체의 기능을 분석하기 위하여 556번째의 아미노산 (D)을 Y로 치환한 돌연변이 수용체 (D556Y)를 만들었다. 이러한 돌연변이 수용체를 동물세포에 발현시켜 cAMP의 분석결과 Ligand (호르몬)가 없어도 지속적으로 정보전달을 세포내부로 보내 cAMP 발현을 현저히 증가시켰다. 따라서 남성의 조기성숙과 관련된 질환은 지속적으로 발현하는 LH /CGR에 의한 원인 때문일 것이다.

• Journal of Microbiology
• /
• 제44권2호
• /
• pp.217-225
• /
• 2006

Kaposi's sarcoma-associated herpesvirus (KSHV) RTA transcription factor is recruited to its responsive elements through interaction with RBP-Jk that is a downstream transcription factor of the Notch signaling pathway that is important in development and cell fate determination. This suggests that KSHV RTA mimics cellular Notch signal transduction to activate viral lytic gene expression. Here, I demonstrated that unlike other B lymphoma cells, KSHV -infected primary effusion lymphoma BCBL1 cells displayed the constitutive activation of ligand-mediated Notch signal transduction, evidenced by the Jagged ligand expression and the complete proteolytic process of Notch receptor I. In order to investigate the effect of Notch signal transduction on KSHV gene expression, human Notch intracellular (hNIC) domain that constitutively activates RBP-Jk transcription factor activity was expressed in BCBL1 cells, TRExBCBL1-hNIC, in a tetracycline inducible manner. Gene expression profiling showed that like RTA, hNIC robustly induced expression of a number of viral genes including KS immune modulatory gene resulting in downregulation of MHC I and CD54 surface expression. Finally, the genetic analysis of KSHV genome demonstrated that the hNIC-mediated expression of KS during viral latency consequently conferred the downregulation of MHC I and CD54 surface expression. These results indicate that cellular. Notch signal transduction provides a novel expression profiling of KSHV immune deregulatory gene that consequently confers the escape of host immune surveillance during viral latency.

• Computers and Concrete
• /
• 제32권5호
• /
• pp.499-511
• /
• 2023

Anchor channels are commonly used for façade, tunnel, and structural connections. These connections encounter various types of loadings during their service life, including high rate or impact loading. For anchor channels that are placed close and parallel to an edge and loaded in shear perpendicular to and towards the edge, the failure is often governed by concrete edge breakout. This study investigates the transverse shear behavior of the anchor channels under quasi-static and high rate loadings using a numerical approach (3D finite element analysis) utilizing a rate-sensitive microplane model for concrete as constitutive law. Following the validation of the numerical model against a test performed under quasi-static loading, the rate-sensitive static, and rate-sensitive dynamic analyses are performed for various displacement loading rates varying from moderately high to impact. The increment in resistance due to the high loading rate is evaluated using the dynamic increase factor (DIF). Furthermore, it is shown that the failure mode of the anchor channel changes from global concrete edge failure to local concrete crushing due to the activation of structural inertia at high displacement loading rates. The research outcomes could be valuable for application in various types of connection systems where a high rate of loading is expected.

• 대한골관절종양학회지
• /
• 제15권2호
• /
• pp.130-137
• /
• 2009

목적: STAT3는 주요 세포 진행과정을 조절하는 암유전자로, 활성화되면 여러 악성종양의 생물학적, 임상적 특징과 연관된다고 알려져 있고, 한편 배아줄기세포와 연관된 유전자이기도 하다. 본 연구에서는 연골종양의 발생에 STAT3 활성화가 관여하는지 살펴보았다. 대상 및 방법: 총 33예의 각종 양성 및 악성 연골종양에서 STAT3 활성화를 살펴보기 위해 활성화된 $pSTAT3^{tyr705}$에 특이한 단클론성 항체를 이용한 면역조직화학법을 시행하였다. 결과: 통상적인 연골육종 17예 중, 조직학적 등급 3의 연골육종은 3예(50%)에서 pSTAT3에 양성이었고, 등급 1 및 2 연골육종은 모두 음성이었다. 즉 pSTAT3 양성도는 조직학적 등급과 통계학적으로 유의한 상관관계(p=0.0432)를 나타내었다. 또한 투명세포 연골육종 2예(50%)도 pSTAT3에 양성이었다. 내연골종, 연골모세포종, 연골점액양섬유종 등 12예의 양성 연골종양 중 6예(50%)에서 pSTAT3가 관찰되었다. 결론: STAT3 활성화는 통상적인 연골육종 중 고도의 조직학적 분화도가 나쁜 등급에서 주로 발견된다. 배아줄기세포 표지자인 STAT3가 양성 및 악성 연골종양 일부에서 활성화되는 것으로 미루어보아 연골 기원 종양에서도 악성종양의 줄기세포 가설을 제안할 수 있다.

• 대한의생명과학회지
• /
• 제9권2호
• /
• pp.59-65
• /
• 2003

When cells are exposed to proteotoxic stresses such as heat shock, amino acid analogs, and heavy metals, they increase the synthesis of the heat shock proteins (HSPs) by activating the heat shock transcription factor 1 (HSF1), whose activity is controlled via multiple steps including homotrimerization, nuclear translocation, DNA binding, and hyperphosphorylation. Under unstressed conditions, the HSF1 activity is repressed through its constitutive phosphorylation by glycogen synthase kinase 3$\beta$ (GSK3$\beta$), extracellular regulated kinase 1/2 (ERK1/2), and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK). However, the protein kinase (s) responsible for HSF1 hyperphosphorylation and activation is not yet identified. In the present study, we observed that profile of p38 mitogen-activated protein kinase (p38MAPK) activation in response to heat shock was very similar to those of HSF1 hyperphosphorylation and nuclear translocation. Therefore, we investigated whether p38MAPK is involved in the heat shock-induced HSF1 activation and HSP expression. Here we show that the p38MAPK inhibitors, SB202190 and SB203580, but not other inhibitors including the MEK1/2 inhibitor PD98059 and the PI3-K inhibitor LY294002 and wortmannin, suppress HSF1 hyperphosphorylation in response to heat shock and L-azetidine 2-carboxylic acid (Azc), but not to heavy metals. Furthermore, heat shock-induced HSF1-DNA binding and HSP72 expression was specifically prevented by the p38MAPK inhibitors, but not by the MEK1/2 inhibitor and the PI3-K inhibitors. These results suggest that SB202190- and SB203580-sensitive p38MAPK may positively regulate HSP gene regulation in response to heat shock and amino acid analogs.

• 생명과학회지
• /
• 제26권9호
• /
• pp.991-998
• /
• 2016

NF-κB는 anti-apoptotic gene을 유도하는 전사인자로서 대부분의 세포의 생존에 필요하다. 그러나 NF-κB가 많은 종류의 암세포에서 지속적으로 과다 활성화됨이 알려지면서 NF-κB의 활성억제가 암의 예방과 치료에 유효하다는 점이 알려지게 되었다. 한편, Hsp70가 NF-κB의 활성을 조절한다는 사실이 알려지면서 Hsp70를 이용한 암예방과 치료가 주목받게 되었으나 아직 Hsp70에 의한 NF-κB의 활성조절기전은 명확하지 않다. 본 연구에서는 Hsp70에 의한 NF-κB의 활성조절과정에서 IKK complex의 구성성분인 IKKγ의 역할을 검토하였다. IKKγ의 wild type과 deletion mutants를 이용하여 Hsp70와 관련된 NF-κB의 활성조절을 연구한 결과 Hsp70는 NF-κB의 활성화를 억제하였으며, 이러한 억제효과는 IKKγ가 과발현되었을 때 더욱 증가하였다. 또한 IKKγ의 N-말단의 IKKβ 결합부위와 C-말단의 Leucine zipper 및 Zinc finger부위는 Hsp70와 연관된 NF-κB억제작용에 필요하지 않는 것으로 나타났으며, Hsp70와 IKKγ에 의한 NF-κB의 활성억제는 IκBα의 인산화와 분해를 저해함에 의해 일어나는 것으로 나타났다. 또한 RAW264.7 macrophage세포에서 LPS에 의한 COX-2의 발현유도는 Hsp70와 IKKγ가 동시에 발현 되었을 때 가장 효과적으로 억제되었다. 이상의 결과로부터 Hsp70에 의한 NF-κB의 활성억제작용은 IKKγ에 의해 상승됨을 알 수 있었으며, Hsp70와 IKKγ를 적절히 이용하면 NF-κB의 과다활성에 의해 발생하는 각종 질병의 예방과 치료에 도움을 줄 수 있을 것으로 기대된다.

• Clinical and Experimental Pediatrics
• /
• 제48권3호
• /
• pp.337-341
• /
• 2005

선천성 갑상선 항진증은 드문 질환으로 모체로부터 TSH에 대한 자가항체가 태반을 통해 태아에게 전달되어 생기며 일시적인 경우가 많다. 선천성 갑상선 항진증이 지속되지만 자가면역질환의 검사 소견을 보이지 않을 때에는 TSHR의 돌연변이에 의한 갑상선 항진증을 고려해야 한다. 저자들은 TSHR의 돌연변이에 의한 갑상선 항진증 증례를 2례 경험하였기에 문헌고찰과 함께 보고하는 바이다.

• 대한의생명과학회지
• /
• 제19권2호
• /
• pp.118-123
• /
• 2013

Tumor necrosis factor-alpha (TNF-${\alpha}$) is a proinflammatory cytokine that mediates the inflammatory response and immune functions, and modulates the proliferation, differentiation and cell death of cancer cells. The differential functions of TNF-${\alpha}$ in various human cells due to the formation of different stimulating pathway upon the binding of TNF-${\alpha}$ to its receptors. In the present study, we examined the different effects of TNF-${\alpha}$ on the survival and apoptosis between normal granulocytes and human myeloid leukemia HL-60 cells. Although TNF-${\alpha}$ did not affect on the constitutive apoptosis of granulocytes, TNF-${\alpha}$ strongly induced the apoptosis of HL-60 cells in a dose- and a time-dependent manner. TNF-${\alpha}$-induced apoptosis was occurred via the activation of caspase 8, caspase 9 and caspase 3/7 and the induction of ROS production in HL-60 cells. Also, BAY-11-7085, a NF-${\kappa}B$ inhibitor, blocked the TNF-${\alpha}$-induced apoptosis in HL-60 cells. NF-${\kappa}B$ may be involved in TNF-${\alpha}$-induced apoptotic signaling pathway in HL-60 cells. These results suggest that TNF-${\alpha}$ activates apoptotic pathways and its process depends on cell type and many cellular factors. A better understanding of the differential effect of TNF-${\alpha}$ on cell apoptosis and survival may provide important information that can be used to elucidate the specific inhibitory effect of TNF-${\alpha}$ on the cancer dis.

• 한국식물병리학회:학술대회논문집
• /
• 한국식물병리학회 2003년도 정기총회 및 추계학술발표회
• /
• pp.79.2-80
• /
• 2003

To better understand plant defense responses against pathogen attack, we identified the transcription factor-encoding genes in the hot pepper Capsicum annuum that show altered expression patterns during the hypersensitive response raised by challenge with bacterial pathogens. One of these genes, Ca1244, was characterized further. This gene encodes a plant-specific Type IIIA - zinc finger protein that contains two Cys$_2$His$_2$zinc fingers. Ca1244 expression is rapidly and specifically induced when pepper plants are challenged with bacterial pathogens to which they are resistant. In contrast, challenge with a pathogen to which the plants are susceptible only generates weak Ca1244 expression. Ca1244 expression is also strongly induced in pepper leaves by the exogenous application of ethephon, an ethylene releasing compound. Whereas, salicylic acid and methyl jasmonate had moderate effects. Pepper protoplasts expressing a Ca1244-smGFP fusion protein showed Ca1244 localizes in the nucleus. Transgenic tobacco plants overexpressing Ca1244 driven by the CaMV 355 promoter show increased resistance to challenge with a tobacco-specific bacterial pathogen. These plants also showed constitutive upregulation of the expression of multiple defense-related genes. These observations provide the first evidence that an Type IIIA - zinc finger protein, Ca1244, plays a crucial role in the activation of the pathogen defense response in plants.

• 한국군사과학기술학회지
• /
• 제7권4호
• /
• pp.70-78
• /
• 2004

A study has been made to investigate the high temperature deformation behavior of Ti-6Al-4V alloyand to predict the final microstructure under given forming conditions. Equiaxed and $Widmanst\ddot{a}tten$ microstructures of Ti-6Al-4V alloys were prepared as initial microstructures. By performing the compression tests at high temperatures$(700\~1100^{\circ}C)$ and at a wide range of strain rates$(10^{-4}\~10^2/s)$, various parameters such as strain rate sensitivity(m) and activation energy(Q) were calculated and used to establish constitutive equations. When the specimens were deformed up to strain 0.6, equiaxed microstructure did not show any significant changes in microstructure, while $Widmanst\ddot{a}tten$ microstructure revealed considerable flow softening, which was attributed to the globularization of a platelet at the temperature range of $800\~970^{\circ}C$ and at the strain rate range of $10^{-4}\~10^{-2}/s$. To predict the final microstructure after forming, finite element analysis was performed considering the microstructural evolution during the deformation. The grain size and the volume fraction of second phase of deformed body were predicted and compared with the experimental results.