Control of Cellular Bcl-x_L Levels by Deamidation-Regulated Degradation

Dho, So Hee,Deverman, Benjamin E.,Lapid, Carlo,Manson, Scott R.,Gan, Lu,Riehm, Jacob J.,Aurora, Rajeev,Kwon, Ki-Sun,Weintraub, Steven J. Public Library of Science 2013 PLoS biology Vol.11 No.6

<P>The cellular concentration of Bcl-x<SUB>L</SUB> is among the most important determinants of treatment response and overall prognosis in a broad range of tumors as well as an important determinant of the cellular response to several forms of tissue injury. We and others have previously shown that human Bcl-x<SUB>L</SUB> undergoes deamidation at two asparaginyl residues and that DNA-damaging antineoplastic agents as well as other stimuli can increase the rate of deamidation. Deamidation results in the replacement of asparginyl residues with aspartyl or isoaspartyl residues. Thus deamidation, like phosphorylation, introduces a negative charge into proteins. Here we show that the level of human Bcl-x<SUB>L</SUB> is constantly modulated by deamidation because deamidation, like phosphorylation in other proteins, activates a conditional PEST sequence to target Bcl-x<SUB>L</SUB> for degradation. Additionally, we show that degradation of deamidated Bcl-x<SUB>L</SUB> is mediated at least in part by calpain. Notably, we present sequence and biochemical data that suggest that deamidation has been conserved from the simplest extant metazoans through the human form of Bcl-x<SUB>L</SUB>, underscoring its importance in Bcl-x<SUB>L</SUB> regulation. Our findings strongly suggest that deamidation-regulated Bcl-x<SUB>L</SUB> degradation is an important component of the cellular rheostat that determines susceptibility to DNA-damaging agents and other death stimuli.</P><P><B>Author Summary</B></P><P>Cellular levels of the pro-survival protein Bcl-x<SUB>L</SUB> are an important determinant of cellular susceptibility to many death stimuli, including most cancer therapies. We previously showed that human Bcl-x<SUB>L</SUB> undergoes deamidation – the conversion of two neutral asparaginyl side-chains into negatively charged aspartyl side-chains – a process that occurs spontaneously but is accelerated by the treatment of tumor cells with DNA-damaging agents. Here, we show that deamidation activates a hitherto undetected signal sequence within Bcl-x<SUB>L</SUB> that targets it for degradation by a pathway involving the proteolytic enzyme calpain. This increased degradation of Bcl-x<SUB>L</SUB>, and the consequent enhanced cellular susceptibility to programmed cell death, may contribute to the ability of DNA-damaging agents to kill tumors. We also demonstrate that deamidation of Bcl-x<SUB>L</SUB> has likely been conserved from the simplest metazoans to humans, underscoring the importance of deamidation in the regulation of Bcl-x<SUB>L</SUB>.</P>

Role of Electrostatic Interaction on the Selective Separation of Oil Emulsion in Wastewater

Dho, Hyon Seung 청주대학교 산업과학연구소 2000 産業科學硏究 Vol.18 No.1

본 연구는 폐수에 용존해 있는 오일 에멀젼과 MF 여과막 표면사이의 발생하는 정전상호작용의 역할에 관한 것이다. 오일 에멀젼의 분리공정에서 파울링 현상은 여과막 표면의 흡착 뿐만아니라, 여과막의 재질 특성, 소수성화와 에멀젼의 안정성과 관계가 있었으며 단순히 여과막의 특성이 파울링에 영향을 주는 것이 아니라는 결론을 얻었다.따라서 파울링 현상은 에멀젼 안정성, 여과막의 표면성질, 계면활성제 농도의 복합적인 관계에서 발생하게 되는 것으로 나타났다. The role of electrostatic interactions between the oil emulsion and membrane surface was investigated. The fouling tendencies in the oil emulsion separation process were correlated not only the excess adsorption on the membrane surface, but also the characteristics of membrane material, hydrophobicity, and emulsion stability. It can be concluded that only membrane surface characteristics have not much influence on fouling behavior contrary to the other investigators. The fouling phenomenon, therefore, may be occurred by the inter change able relationship of the emulsion stability, membrane surface characteristics, surfactant concentrations, and physical characteristics for participating the experiments.

Weight Loss of Poly(ethylene terphthalate)Fiber by Trisodium Phosphate

Dho, Seong-kook,Cho, Hwan 東亞大學校 大學院 1988 大學院論文集 Vol.13 No.-

폴리 에틸렌 텔레프탈레이트 섬유는 우수한 물성 때문에 섬유로서의 효용가치가 크다. 그러나 염색성, 흡습성, 대전성, 촉감 등에 단점이 있다. 특히, 경한 촉감의 개선을 위해서 수산화 나트륨에 의한 감량가공이 행하여지고 있으며 처리 섬유는 촉감 뿐 아니라 흡습성 및 대전성도 다소 개선되는 것으로 알려져 있다. 본 실험은 현재 사용되는 수산화나트륨 이외에 적절한 감량가공을 행할 수 있는 알칼리제를 찾기 위하여 예비실험에서 수종의 알카리제를 사용하였다. 그 결과 트리소디움 포스케이트가 폴리에틸렌 텔레프탈레이트 섬유의 감량가공에 실제 사용될 수 있다고 생각하였다. 몇가지 얻어진 결론은 감량율은 처리시간, 농도, 온도에 따라 증가하였으며 강도는 감소하였다. 감량에 의해 촉감 및 흡습성은 개선되었으나 실용감량율에 도달하는데는 과량의 트리소디움 포스케이트와 장시간이 소요되었다.

External Field Dependence of $Fe^57$ NMR in Pure Iron

Dho, Joongheo,Kim, Mincheol,Lee, Soonchil,Lee, Wonjong,Kim, Yoonbae The Korean Magnetics Society 1996 Journal of Magnetics Vol.1 No.1

The NMR spin echo in pure iron was measured as a function of external magnetic field up to 10 kgauss at room temperature. We observed the signal coming from a single domain formed over 7.5 kgauss which has not been detected in previous works. The resonance frequency shift with external field confirmed that the hyperfine field in iron is -330.2 kgauss. From the comparison of the magnetization curve with the domain wall signal and the resonance frequency in external field, we showed that NMR could give the useful qualitative information on the magnetization process. The extent of the internal strain removed by annealing, which can be hardly seen in hysteresis curves, was clearly shown up in the NMR line-width.

Optimal strategy of gamma knife radiosurgery for craniopharyngiomas

Dho, Yun-Sik,Kim, Yong Hwy,Kim, Jin Wook,Park, Chul-Kee,Chung, Hyun-Tai,Kim, Seung-Ki,Paek, Sun Ha,Wang, Kyu-Chang,Kim, Dong Gyu Springer-Verlag 2018 Journal of neuro-oncology Vol.140 No.1

Flotation Kinetics-Schuhmann's Modelling and Experimental Study

Dho, Hyon Seung 청주대학교 산업과학연구소 1997 産業科學硏究 Vol.15 No.2

Schuhmann의 속도 modelling을 인회석의 연속 부선 실험결과에 적용하였다. batch나 semi-batch 형태의 부선 실험과 달리 연속 부선 cell을 이용시 인회석의 부선 상태를 정량적으로 평가할 수 있었다. 실험결과 인회석의 부선에서 밝혀지지 않았던 규산나트륨의 역할은 특정 부선 속도와 인회석의 광물화 계수를 향상시키고 따라서 상대 부선 속도를 증가시킴을 정량적으로 평가할 수 있었다.

Endoscopic endonasal approach for craniopharyngioma: the importance of the relationship between pituitary stalk and tumor

Dho, Yun-Sik,Kim, Yong Hwy,Se, Young-Bem,Han, Doo Hee,Kim, Jung Hee,Park, Chul-Kee,Wang, Kyu-Chang,Kim, Dong Gyu American Association of Neurological Surgeons 2018 Journal of Neurosurgery Vol.129 No.3

<B>OBJECTIVE</B><P>The endoscopic endonasal approach (EEA) is commonly used for the treatment of craniopharyngioma; therefore, it is essential to analyze outcomes in order to understand the benefits and drawbacks. The goal of this paper was to evaluate the clinical features and outcomes associated with this treatment approach.</P><B>METHODS</B><P>From July 2010 to March 2016, 82 adult craniopharyngioma patients underwent an EEA at the authors’ institution. Of these cases, intraoperative records and immediate postoperative MR images were available for 68 patients. The patients underwent systemized endocrinological evaluation. Eighteen of 68 patients who underwent EEA for recurrence or regrowth of residual lesions after previous surgical management were excluded in the analysis of the anatomical tumor classification. The authors retrospectively analyzed preoperative clinical features and previous anatomical classifications, focusing on the relationship of the pituitary stalk and tumor, to determine predictive factors for the clinical outcome, such as the extent of resection, visual function, endocrinological function, recurrence rate, and complications.</P><B>RESULTS</B><P>The mean tumor size was 2.5 cm (3.1 cm for primary tumors and 1.9 cm for recurrent lesions). Gross-total resection (GTR) was achieved in 62 (91.1%) patients (48 [96.0%] patients with primary tumors and 14 [77.8%] patients with recurrent tumors). The rate of GTR was higher in the primary group than in the group with recurrence (p = 0.038). The overall pre- and postoperative visual impairment scale (VIS) scores were 40.8 and 22.1, respectively (50.9 and 14.3 in the primary group and 30.7 and 29.9 in patients with recurrence, respectively). The improvement rate in VIS score was higher in the primary group than in the recurrent group (p = 0.001). Endocrinological function was improved in 4 patients (5.9%) and deteriorated in 32 of 68 patients (47.1%). Tumor invasion into the center of the pituitary stalk affected the postoperative outcomes most significantly. Cognitive dysfunction was observed in 22 patients before surgery and improved in 20 patients (90.9%) after surgery. Hydrocephalus was found in 7 patients and resolved after surgery in all cases. CSF leakage occurred in 2 (2.9%) of 68 patients and was repaired by revision surgery in both patients. Ten patients without CSF leakage also received antibiotics for the treatment of meningitis. The infection rate was higher in the recurrent group. Postoperative endocrinological evaluation showed no deficits in 12 patients and panhypopituitarism in 55 patients. The remaining patient had growth hormone deficiency. Forty-three patients had new-onset diabetes insipidus, and 1 patient had persistent diabetes insipidus after surgery. There were 2 (2.9%) cases of recurrence during the mean 30.7-month follow-up period; one patient underwent radiosurgery and the other underwent reoperation.</P><B>CONCLUSIONS</B><P>The EEA resulted in excellent surgical outcomes and acceptable morbidity rates, regardless of the anatomical location of the tumor. Invasion of the craniopharyngioma into the center of the pituitary stalk has strong predictive power for postoperative endocrinological outcome.</P>

Investigation of the location of atypical teratoid/rhabdoid tumor.

Dho, Yun-Sik,Kim, Seung-Ki,Cheon, Jung-Eun,Park, Sung-Hye,Wang, Kyu-Chang,Lee, Ji Yeoun,Phi, Ji Hoon Springer Verlag 2015 Child's nervous system Vol.31 No.8

<P>The location of a brain tumor is a fundamental characteristic, because various brain tumors develop in relatively specific locations. An atypical teratoid/rhabdoid tumor (AT/RT) is a highly age-specific tumor that occurs in infants and young children. However, AT/RTs develop in a variety of locations in the brain. This study aimed at uncovering the tumor location pattern of AT/RTs to enhance diagnoses.</P>

Interface Reaction and Thickness-dependent Spin-diffusion Effect in YBa2Cu3O7- /La0.7Sr0.3MnO3 Bilayers

Dho, Joonghoe,Ki, Sanghoon Korean Physical Society 2010 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.57 No.6

Catastrophic Intramedullary Abscess Caused by a Missed Congenital Dermal Sinus

Dho, Yun-Sik,Kim, Seung-Ki,Wang, Kyu-Chang,Phi, Ji Hoon The Korean Neurosurgical Society 2015 Journal of Korean neurosurgical society Vol.57 No.3

Congenital dermal sinus (CDS) is a type of occult spinal dysraphism characterized by a midline skin dimple. A 12-month-old girl presented with fever and ascending quadriparesis. She had a midline skin dimple in the upper sacral area that had been discovered in her neonatal period. Imaging studies revealed a holocord intramedullary abscess and CDS. Overlooking CDS or misdiagnosing it as benign sacrococcygeal dimple may lead to catastrophic infection and cause serious neurological deficits. Therefore, further imaging work-up or consultation with a pediatric neurosurgeon is recommended following discovery of any atypical-looking dimples in the midline.