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Network perturbation by recurrent regulatory variants in cancer
Jang, Kiwon,Kim, Kwoneel,Cho, Ara,Lee, Insuk,Choi, Jung Kyoon Public Library of Science 2017 PLoS computational biology Vol.13 No.3
<▼1><P>Cancer driving genes have been identified as recurrently affected by variants that alter protein-coding sequences. However, a majority of cancer variants arise in noncoding regions, and some of them are thought to play a critical role through transcriptional perturbation. Here we identified putative transcriptional driver genes based on combinatorial variant recurrence in <I>cis</I>-regulatory regions. The identified genes showed high connectivity in the cancer type-specific transcription regulatory network, with high outdegree and many downstream genes, highlighting their causative role during tumorigenesis. In the protein interactome, the identified transcriptional drivers were not as highly connected as coding driver genes but appeared to form a network module centered on the coding drivers. The coding and regulatory variants associated via these interactions between the coding and transcriptional drivers showed exclusive and complementary occurrence patterns across tumor samples. Transcriptional cancer drivers may act through an extensive perturbation of the regulatory network and by altering protein network modules through interactions with coding driver genes.</P></▼1><▼2><P><B>Author summary</B></P><P>Identifying driver variants is a current challenge facing cancer genomics. A well-established and robust method for this is to find recurrence in large cohorts of samples. Recurrence patterns of amino acid-changing variants can reveal oncogenes and tumor suppressor genes. However, such single-gene approaches have limitations because of rare variants. Therefore, recurrently affected protein complexes, network modules, or signaling pathways have been identified based on network-level recurrence. Here we dissect chromatin interactome to identify <I>cis</I>-regulatory variants that show high gene-level recurrence. We then employ the gene regulatory network and protein interactome to characterize putative cancer genes with <I>cis</I>-regulatory variant recurrence. These genes were located at critical positions in the regulatory network. By contrast, they are at the circumference in the protein interactome; instead, they form a network module with coding cancer genes located at hub positions. Furthermore, the coding and regulatory variants associated via these interactions showed exclusive and complementary occurrence patterns across tumor samples. Therefore, we suggest that transcriptional cancer drivers may act through an extensive perturbation of the regulatory network and by altering protein network modules through interactions with coding driver genes.</P></▼2>
ByongSu Jang,Hyeran Kim,ShinnWon Lim,KiWon Jang,DohKwan Kim 대한신경정신의학회 2008 PSYCHIATRY INVESTIGATION Vol.5 No.3
Objective-S100B is a neurotrophic factor that is involved in neuroplasticity. Neuroplasticity is disrupted in depression; however, treatment with antidepressants can restore neuroplasticity. S100B has previously been used as a biological marker for neuropathology and neuroplasticity; therefore, in this study, we compared serum S100B levels in depressive patients to those of normal controls. In addition, we compared the serum S100B levels of antidepressant responders to those of nonresponders. Methods-Thirty five normal controls and 59 depressive patients were enrolled in this study. Depressive patients entered a 6 week clinical trial that included treatment with antidepressants. The serum S100B levels and clinical assessments, which included Hamilton depression rating scores, were measured at baseline and after 6 weeks of treatment with antidepressants. The difference in the serum S100B levels between depressive patients and normal controls and between antidepressant responders and nonresponders was then compared. Results-There were no significant differences in the serum S100B levels of normal controls and depressive patients. In addition, 30 of the depressive patients responded to antidepressant treatment while 29 did not. Finally, the responders had significantly higher baseline serum S100B levels than the nonresponders. Conclusion-The results of this study suggest that the baseline serum S100B level is associated with the subsequent response to antidepressants. In addition, the high baseline serum S100B level that was observed in depressive patients may enhance neuroplasticity, which results in a favorable therapeutic response to antidepressants.
Examining Patterns of Polypharmacy in Bipolar Disorder: Findings from the REAP-BD, Korea
Kiwon Kim,Hyunju Yang,Euihyeon Na,Hoseon Lee,Ok-Jin Jang,Hyung-Jun Yoon,Hong Seok Oh,Byung-Joo Ham,Seon-Cheol Park,Shih-Ku Lin,Chay Hoon Tan,Naotaka Shinfuku,Yong Chon Park 대한신경정신의학회 2019 PSYCHIATRY INVESTIGATION Vol.16 No.5
Based on Korean data from the Research on Asian Psychotropic Prescription Pattern for Bipolar Disorder, this study tried to present prescription patterns in biopolar disorder (BD) and its associated clinical features. Based on the information obtained from the study with structured questions, the tendency of prescription pattern was studied and analyzed. Polypharmacy was predominant, including simple polypharmacy in 51.1% and complex polypharmacy in 34.2% of patients. Subjects associated with simple or complex polypharmacy were significantly younger, had higher inpatient settings, a larger portion of onset with manic episode, a shorter duration of untreated illness, a shorter duration of current episode, were more overweight, used less antidepressants and used more anxiolytics. These findings can suggest higher polypharmacy rate in more severe BD and highlight the necessity of monitoring the weight of subjects with polypharmacy.
( Jiwoong Jang ),( Hea Yeon Yun ),( Jonghoon Park ),( Kiwon Lim ) 한국운동영양학회 2015 Physical Activity and Nutrition (Phys Act Nutr) Vol.19 No.3
[Purpose] The effect of BCAA (branched chain amino acid) administration on muscle atrophy during growth phases is not well known. We investigated whether BCAA administration can prevent the muscle atrophy induced by hindlimb suspension in growing male rats. [Methods] MaleWistar rats were assigned to 1 of 2 groups (n = 7/group): hindlimb suspension and hindlimb suspension with oral BCAA administration (600 mg·kg-1·day-1, valine 1: leucine 2: isoleucine 1). After 14 days of hindlimb suspension, the weight and mRNA levels of the soleus muscle were measured. [Results] BCAA administration prevented a decrease in soleus muscle weight. BCAA administration attenuated atrogin-1 and MuRF1 mRNA expression, which has been reported to play a pivotal role in muscle atrophy. [Conclusion] BCAA could serve as an effective supplement for the prevention or treatment of muscle atrophy, especially atrophy caused by weightlessness.
( Jiwoong Jang ),( Hun-young Park ),( Choongsung Yoo ),( Yeram Park ),( Jisu Kim ),( Kiwon Lim ) 한국운동영양학회 2017 Physical Activity and Nutrition (Phys Act Nutr) Vol.21 No.4
[Purpose] Resistance exercise training (RET) and an additional intake of dietary protein supplements may improve muscle mass and muscular function, and reduce inflammatory markers. The types, amount, and timing of dietary protein supplements are important for the synergistic effects of resistance training and dietary protein supplements. We hypothesized that a 25.1 g protein complex supplement taken for 12 weeks, immediately before and after resistance exercise, would enhance fat free mass and isokinetic muscular function in young untrained males. [Methods] Eighteen participants were randomly assigned to a placebo (n=8) or protein complex supplement groups (n=10). The RET was a supervised progressive program, 3 times per week for 12-weeks, and was performed progressing 80% of their one repetition maximum (1-RM). Body composition, blood pressure, plasma inflammatory markers, lipid level and isokinetic muscular function were assessed before and after the study period. [Results] There was a significant interaction effect in C-reactive protein (CRP) (p =0.044) among blood vessel inflammatory markers. The protein complex supplement group had shown more effective improvement at 12 weeks intervention compared to the placebo group in isokinetic muscular function. There was a significant interaction effect in peak torque at 60 degrees/sec leg extension (p =0.044), total work at 240 degrees/sec leg extension (p =0.025), and total work at 240 degrees/sec leg flexion (p =0.011). [Conclusion] Protein complex supplementation during RET appears more effective than RET alone in improving isokinetic muscular function for 12 weeks in untrained young men.
이기원(Kiwon Lee),김주락(Joorak Kim),장동옥(Donguk Jang) 한국철도학회 2004 한국철도학회 학술발표대회논문집 Vol.- No.-
Railway safety is based on a risk analysis and safety assessment for the whole railway system as human, train, electric, signaling, operation, maintenance and etc. Therefore in this study, after investigating the accidents happened in electric railway on Choongang line for 5 years, from "97 to "01, a Data-Base was made through a cause and result analysis. In consideration of economic loss and human resources damage, a risk assessment for electric railway was also performed.