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MafB negatively regulates RANKL-mediated osteoclast differentiation
Kim, Kabsun,Kim, Jung Ha,Lee, Junwon,Jin, Hye Mi,Kook, Hyun,Kim, Kyung Keun,Lee, Soo Young,Kim, Nacksung American Society of Hematology 2007 Blood Vol.109 No.8
<B>Abstract</B><P>Receptor activator of nuclear factor κB ligand (RANKL) induces osteoclast formation from hematopoietic cells via regulation of various transcription factors. Here, we show that MafB negatively regulates RANKL-induced osteoclast differentiation. Expression levels of MafB are significantly reduced by RANKL during osteoclastogenesis. Overexpression of MafB in bone marrow-derived monocyte/macrophage lineage cells (BMMs) inhibits the formation of TRAP+ multinuclear osteoclasts, but phagocytic activity of BMMs is retained. Furthermore, overexpression of MafB in BMMs attenuates the gene induction of NFATc1 and osteoclast-associated receptor (OSCAR) during RANKL-mediated osteoclastogenesis. In addition, MafB proteins interfere with the DNA-binding ability of c-Fos, Mitf, and NFATc1, inhibiting their transactivation of NFATc1 and OSCAR. Furthermore, reduced expression of MafB by RNAi enhances osteoclastogenesis and increases expression of NFATc1 and OSCAR. Taken together, our results suggest that MafB can act as an important modulator of RANKL-mediated osteoclastogenesis.</P>
( Junwon Kim ),( Jang Hun Kim ),( Jong Hyun Kim ),( Taek-hyun Kwon ),( Haewon Roh ) 대한외상학회 2019 大韓外傷學會誌 Vol.32 No.4
Purpose: Cranioplasty (CP) is often required for survival after decompressive craniectomy. Several materials, including autologous bone and various artificial materials, have been introduced for CP, but it remains unclear which material is best for CP. This study aimed to explore differences in complications between patients who underwent CP using an autologous bone flap versus a three-dimensional (3D) titanium mesh and to identify significant risk factors for post-CP complications. Methods: In total, 44 patients were enrolled in this study and divided into two groups (autologous bone vs. 3D titanium mesh). In both groups, various post-CP complications were evaluated. Through a comparative analysis, we aimed to identify differences in complications between the two groups and, using binary logistic analysis, to determine significant factors associated with complications after CP. Results: In the autologous bone flap group, there were three cases of surgical infection (3/24, 12.5%) and 11 cases of bone flap resorption (BFR) (11/24, 45.83%). In the 3D titanium mesh group, there was only one case of surgical infection (1/20, 5%) and 11 cases of various complications, including mainly cosmetic issues (11/20, 55%). A subgroup risk factor analysis of CP with an autologous bone f lap showed no risk factors that predicted BFR with statistical significance, although a marginal association was found between larger bone flaps and BFR (odds ratio [OR]=1.037, p=0.090). In patients treated with a 3D titanium mesh, multivariate analysis revealed that only the existence of a ventriculo-peritoneal shunt system was strongly associated with overall post-CP complications (OR=18.66, p=0.021). Conclusions: Depending on which material was used, different complications could occur, and the rate of complications was relatively high in both groups. Hence, the material selected for CP should be selected based on individual patients’ conditions.
강태웅(Taewoong Kang),김재원(Jae-Won Kim),반건호(Geon Ho Bahn),송숙형(Sook Hyung Song),김준원(Junwon Kim),김지훈(Ji-Hoon Kim),김윤정(Yoon-Jung Kim),김의정(Eui-Jung Kim),김태호(Tae-Ho Kim),양수진(Su-Jin Yang),양재원(Jaewon Yang),이소영(S 대한소아청소년정신의학회 2015 소아청소년정신의학 Vol.26 No.4
Objectives:Symptoms of attention-deficit hyperactivity disorder (ADHD) during childhood may persist into adulthood. This study included the development and validation process of the Korean Adult ADHD Rating Scale (K-AARS), which was developed for screening and monitoring treatment of adults with ADHD. Methods:Preliminary questionnaires of the K-AARS were based on the reviews of previous adult ADHD scales and clinical experiences of the board certified child and adolescent psychiatrists in Korea. For this study, 136 adults (18–50 years old) with inattention, hyperactivity and/or impulsivity symptoms were enrolled as ADHD subjects, and compared with 406 control subjects (18–50 years old) without ADHD symptoms. Construct validity was examined using explorative factor analysis and Cronbach’s alpha to obtain internal reliability coefficients. Concurrent validity was evaluated by comparison with the Conners’ Adult ADHD Rating Scale (CAARS). Results:An explorative factor analysis showed that the K-AARS had 8 factors (inattention, hyperactivity, impulsivity, antisocial personality disorder/conduct disorder/oppositional defiant disorder, impairment, driving, emotional dysregulation, disorganization). K-AARS was highly reliable in terms of internal consistency (Cronbach’s alpha 0.77–0.95) and correlation between factors (0.57–0.86). Concurrent validity with the CAARS and discriminant validity were statistically significant. Conclusion:The K-AARS is a valid and reliable measure for assessment of Korean adults with ADHD.
Cdc5-Dependent Asymmetric Localization of Bfa1 Fine-Tunes Timely Mitotic Exit
Kim, Junwon,Luo, Guangming,Bahk, Young Yil,Song, Kiwon Public Library of Science 2012 PLoS genetics Vol.8 No.1
<▼1><P>In budding yeast, the major regulator of the mitotic exit network (MEN) is Tem1, a GTPase, which is inhibited by the GTPase-activating protein (GAP), Bfa1/Bub2. Asymmetric Bfa1 localization to the bud-directed spindle pole body (SPB) during metaphase also controls mitotic exit, but the molecular mechanism and function of this localization are not well understood, particularly in unperturbed cells. We identified four novel Cdc5 target residues within the Bfa1 C-terminus: <SUP>452</SUP>S, <SUP>453</SUP>S, <SUP>454</SUP>S, and <SUP>559</SUP>S. A Bfa1 mutant in which all of these residues had been changed to alanine (Bfa1<SUP>4A</SUP>) persisted on both SPBs at anaphase and was hypo-phosphorylated, despite retaining its GAP activity for Tem1. A Bfa1 phospho-mimetic mutant in which all of these residues were switched to aspartate (Bfa1<SUP>4D</SUP>) always localized asymmetrically to the SPB. These observations demonstrate that asymmetric localization of Bfa1 is tightly linked to its Cdc5-dependent phosphorylation, but not to its GAP activity. Consistent with this, in kinase-defective <I>cdc5-2</I> cells Bfa1 was not phosphorylated and localized to both SPBs, whereas Bfa1<SUP>4D</SUP> was asymmetrically localized. <I>BFA1<SUP>4A</SUP></I> cells progressed through anaphase normally but displayed delayed mitotic exit in unperturbed cell cycles, while <I>BFA1<SUP>4D</SUP></I> cells underwent mitotic exit with the same kinetics as wild-type cells. We suggest that Cdc5 induces the asymmetric distribution of Bfa1 to the bud-directed SPB independently of Bfa1 GAP activity at anaphase and that Bfa1 asymmetry fine-tunes the timing of MEN activation in unperturbed cell cycles.</P></▼1><▼2><P><B>Author Summary</B></P><P>During mitosis the replicated chromosomes are distributed equally to the daughter cells. Once the chromosomes have segregated properly, a pathway called the mitotic exit network (MEN) becomes activated to complete mitosis. How MEN activation is coordinated with segregation of the chromosomes is currently a focus of interest. In budding yeast, Tem1 initiates MEN activation and Bfa1 negatively regulates Tem1 with Bub2. The polo kinase Cdc5 also activates MEN by directly phosphorylating and inhibiting Bfa1. The spindle pole body (SPB), which corresponds to the mammalian centrosome, acts as a platform for these MEN components. The Bfa1/Bub2 complex localizes to SPBs and regulates the association of Tem1 with the SPBs. When the spindle aligns correctly along the mother-bud axis, Bfa1/Bub2 is restricted to the bud-oriented SPB. Conversely, when the spindle is misaligned, Bfa1/Bub2 is present on both SPBs and mitotic exit is delayed, suggesting that the spatial distribution of Bfa1/Bub2 controls the timing of mitotic exit. In this study, we identified new Cdc5 target phosphorylation residues in Bfa1 that function in its asymmetric distribution on SPBs and showed that the asymmetric Bfa1 distribution was required for timely mitotic exit during unperturbed cell cycle of the budding yeast.</P></▼2>